RARE DISEASE
Thymic carcinoma
Thymic carcinoma
Thymic carcinoma
Synonyms: Malignant thymoma
Synonyms: Malignant thymoma
Synonyms: Malignant thymoma
Drug discovery
1
drug
With orphan designation
Overview
Thymic carcinoma is a rare, aggressive mediastinal malignancy arising from thymic epithelial cells, accounting for 0.07–0.38 cases per 100,000 annually [2][5][12]. It typically presents with locally invasive or metastatic disease, necessitating multimodal treatment. Histologically distinct from thymoma, it demonstrates poor differentiation and frequent TP53 mutations [5][16].
Therapies
Surgery: First-line for resectable tumors, often combined with adjuvant radiotherapy (50–75% 5-year survival post-R0 resection) [5][8]
Systemic therapy: Platinum-based regimens (e.g., carboplatin/paclitaxel) for advanced disease; emerging role for lenvatinib/pembrolizumab combinations [3][13][16]
Radiation: Used neoadjuvantly, adjuvantly, or palliatively; improves local control in incompletely resected cases [5][8]
Categories: rare neoplastic diseases
Research Papers
1,458 drug discovery papers about Thymic carcinoma, with 1 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
1,458 drug discovery papers about Thymic carcinoma, with 1 first-in-class and 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-27 | Healing of Post-Operative Tracheal Disruption in a Patient with Thymic Carcinoma on Adjuvant Immunotherapy.
Pneumomediastinum from tracheal perforations due to primary repair breakdown can occur as a complication of thymic cancer surgery. Immunotherapy may be a viable adjuvant treatment for thymic carcinoma patients with tracheal perforations.
2026-09-20 | Advanced thymic epithelial tumours after neoadjuvant therapy: a narrative review of surgical challenges and strategies.
Thymic epithelial tumours, including thymoma and thymic carcinoma, are rare anterior mediastinal neoplasms. Complete surgical resection remains the strongest prognostic determinant, yet locally advanced disease frequently involves critical mediastinal structures and requires multimodality treatment. Neoadjuvant therapy is commonly used to improve resectability, although it alters operative anatomy in ways that can complicate subsequent surgery. This narrative review offers an updated appraisal of the surgical challenges that arise after neoadjuvant therapy, and of contemporary strategies for complex post-induction resection. A targeted literature search was carried out in PubMed, MEDLINE, Embase, Scopus, Web of Science and Google Scholar for English-language publications from January 1990 through January 2026. Search terms combined thymic malignancies, induction and chemoradiotherapy strategies, surgical resection, vascular reconstruction, pleural disease and survival. Emphasis was placed on contemporary literature (2010 to 2026) to reflect advances in imaging, multimodality therapy and surgical reconstruction. Neoadjuvant therapy produces dense fibrosis and obscures tissue planes, which complicates the dissection of critical structures. Imaging often underestimates stromal remodelling and residual viable tumour, so unexpected intraoperative difficulty is common. Vascular involvement is a major driver of operative complexity and frequently calls for resection and reconstruction, with contemporary graft patency of roughly 85% to 90% at five years in specialised series. In stage III disease, reported five-year survival after complete resection is approximately 70% to 90% for thymoma and 30% to 50% for thymic carcinoma. In stage IVa disease, cytoreductive surgery remains a treatment option when macroscopic complete resection is feasible, but the balance between aggressive procedures such as extrapleural pneumonectomy and more conservative pleurectomy/decortication must be weighed very carefully, since high-quality comparative evidence is lacking. Emerging data suggest that neoadjuvant chemoradiotherapy may yield higher R0 rates than chemotherapy alone, albeit at the cost of more pronounced fibrosis, although a matching survival benefit has not yet been proven. Molecular profiling (including GTF2I and TP53/KIT alterations) and AI-assisted imaging biomarkers are increasingly informing patient selection and surgical planning. Surgery after neoadjuvant therapy is feasible and safe in experienced centres, and in selected patients the oncologic outcomes appear to approach those of upfront resection with acceptable postoperative morbidity. Given the rarity of these tumours and the retrospective nature of most of the evidence, however, any comparison with upfront surgery should be interpreted with caution. Future progress will depend on international collaboration, prospective registries, validated molecular and imaging biomarkers, and standardisation of multimodality strategies.
2026-09-11 | Immune checkpoint inhibitors in thymic epithelial tumors: current evidence, immune-related toxicity, and perioperative considerations-a narrative review.
Thymic epithelial tumors (TETs) are rare mediastinal malignancies with unique immunobiological features related to thymic immune tolerance. Although immune checkpoint inhibitors (ICIs) have shown clinical activity, especially in thymic carcinoma, their use is limited by frequent and sometimes severe immune-related adverse events (irAEs), particularly in thymoma. This review summarizes current evidence on the efficacy, toxicity, biomarkers, and perioperative implications of ICIs in TETs. A narrative review was conducted using PubMed, Web of Science, and Embase for English-language studies on ICIs in TETs published from database inception to September 2025. Reference lists of relevant articles and guideline papers were also manually screened. Prospective trials, retrospective cohorts, guideline papers, and key mechanistic studies were prioritized, with emphasis on histology-specific efficacy, irAEs, biomarkers, and perioperative application. Current evidence suggests that ICIs have more consistent antitumor activity in thymic carcinoma than in thymoma. In contrast, thymoma carries a substantially higher risk of severe early irAEs, particularly myocarditis, myositis, and myasthenia gravis overlap syndromes. Biomarkers such as programmed death-ligand 1 (PD-L1) expression and immune-related signatures remain promising but are not yet sufficiently validated for routine patient selection. Perioperative immunotherapy is an emerging strategy, but current evidence remains limited and safety concerns are significant. ICIs represent a promising treatment option for selected patients with advanced TETs, particularly thymic carcinoma, but their clinical use remains restricted by toxicity and limited evidence. Future progress will depend on better risk stratification, biomarker-guided selection, and safer multidisciplinary integration.
2026-08-27 | Real-world outcomes of second-line therapy in advanced thymic carcinoma: a multicenter Turkish Oncology Group (TOG) study
Abstract Background Thymic carcinoma (TC) is a rare and aggressive malignancy with limited evidence guiding second-line treatment after prior systemic therapy. We evaluated real-world outcomes of second-line systemic therapy in a multicenter cohort. Methods Adults with unresectable, recurrent, or metastatic TC who received second-line systemic therapy after prior systemic therapy between 2010 and 2023 were retrospectively analyzed. Treatments were categorized as multidrug chemotherapy, gemcitabine monotherapy, PD-1 inhibitor therapy, or targeted therapy (sunitinib). For the primary comparison of multidrug chemotherapy versus gemcitabine monotherapy, propensity scores based on age, sex, ECOG performance status, Masaoka–Koga stage IV, prior surgery, and calendar year were used to generate overlap weights. Weighted Cox models used robust standard errors clustered by treatment center. A sensitivity propensity-score model additionally included first-line carboplatin–paclitaxel exposure (yes/no). Results A total of 107 patients from 20 treatment centers were included. Median age was 53.2 years (IQR, 41.5–58.0), 78 (72.9%) were male, 81 of 106 patients with available data (76.4%) had ECOG 0–1, and 61 (57.0%) had Masaoka–Koga stage IV disease at diagnosis. At a median follow-up of 35 months, median PFS and OS for the overall cohort were 13.6 and 35.0 months, respectively. In the primary overlap-weighted comparison ( n = 89), multidrug chemotherapy was associated with a lower hazard of progression or death than gemcitabine monotherapy (HR, 0.29; 95% CI, 0.14–0.59; p < 0.001) and a lower hazard of death (HR, 0.42; 95% CI, 0.18–0.97; p = 0.043). In a sensitivity model additionally incorporating first-line carboplatin–paclitaxel exposure, the PFS estimate remained significant (HR, 0.32; 95% CI, 0.16–0.65; p = 0.0015), whereas the OS estimate remained directionally similar but was less precise (HR, 0.46; 95% CI, 0.19–1.11; p = 0.083). The PD-1 inhibitor group ( n = 13) had median PFS and OS of 15.0 and 48.0 months, respectively, in unadjusted descriptive analyses. Conclusions In this retrospective cohort, multidrug chemotherapy was associated with lower hazards of progression or death and of death than gemcitabine monotherapy in the primary overlap-weighted analysis. A sensitivity analysis additionally accounting for first-line carboplatin–paclitaxel exposure preserved the PFS association and yielded a similar but less precise OS estimate. Outcomes observed with PD-1 inhibitors were favorable but should be interpreted descriptively because of the small sample size, later treatment era, and potential residual confounding. These findings are hypothesis-generating and require prospective validation.
2026-08-27 | Robotic-Assisted Extended Thymus Carcinoma Resection With Unilateral Total Pleurectomy and Hyperthermic Intrathoracic Chemotherapy (HITOC).
Thymic squamous cell carcinoma (SCC) is an aggressive form of thymic cancer that is often diagnosed at an advanced stage. Hyperthermic intrathoracic chemotherapy (HITOC) is a treatment option for advanced thoracic and especially pleural malignancies, though it is not yet the standard of care. However, the success of treating pleural cancers with HITOC protocols has been well documented in selected cases. Robotic-assisted thoracoscopic surgery (RATS) has become the standard procedure for thymectomy, even for locally advanced tumors. In this report, we describe the treatment of a 53-year-old patient with a locally advanced Masaoka-Koga stage IVa thymic SCC and concomitant limited pleural carcinomatosis who was successfully treated by RATS thymectomy and HITOC. The report highlights the diagnostic challenges, therapeutic approach, and postoperative care, emphasizing the advantages of minimally invasive, robot-assisted surgery even in advanced cases. RATS with HITOC can be a safe and effective method for the treatment of advanced thymic carcinoma. This case report demonstrates that this procedure enables rapid postoperative recovery and can be performed with minimal morbidity.
antibodies
2026-09-30 | A Case Report of Bilateral Thyroid Thymic Carcinoma with Multiple Cervical Lymph Node Metastases: Clinical Manifestations and Imaging Characteristics.
Intrathyroidal thymic carcinoma (ITTC) is a rare low-grade malignant tumor arising within the thyroid gland. It exhibits histological and immunophenotypic features similar to thymic carcinoma. Due to its rarity and non-specific imaging findings, preoperative diagnosis remains challenging. We report a case of a 60-year-old male who presented with hoarseness and dysphagia. Ultrasound revealed multiple bilateral thyroid nodules with irregular margins and heterogeneous internal echoes, along with bilateral cervical lymphadenopathy. Enhanced CT showed heterogeneous enhancement of the thyroid and enlarged lymph nodes. The patient underwent extended radical resection of bilateral thyroid cancer with mediastinal lymph node dissection. Postoperative pathology and immunohistochemistry confirmed the diagnosis of bilateral thyroid thymic carcinoma with multiple cervical lymph node metastases. ITTC should be considered in the differential diagnosis of thyroid nodules with suspicious ultrasound features, especially when associated with cervical lymph node metastases. Positive expression of CD5 and CD117 with negative expression of Tg and TTF-1 is diagnostic. Treatment follows principles similar to those for thymic carcinoma, and complete surgical resection remains the mainstay.
2026-09-23 | Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.
Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4+/CD8+ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4+/CD8+ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4+/CD8+ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.
2026-09-20 | Anti-angiogenic therapy in thymic carcinoma: a narrative review of current evidence and emerging combinations.
Thymic carcinoma (TC) is a rare and aggressive malignancy with limited systemic treatment options. Although platinum-based chemotherapy has historically been the first-line standard, anti-angiogenic therapy has emerged as an important therapeutic strategy across treatment settings. This review synthesizes current evidence on anti-angiogenic therapies, as monotherapy and in combination with chemotherapy or immunotherapy, and defines their evolving role in TC management. A targeted narrative review was conducted using PubMed/MEDLINE, Embase, Google Scholar, ClinicalTrials.gov, conference proceedings, and reference list screening to identify clinical studies of anti-angiogenic therapy in TC published from January 2000 to January 2026. Anti-angiogenic therapy demonstrates clinical activity across treatment settings in TC. Yet the magnitude and durability of benefit vary by agent, treatment line, and prior vascular endothelial growth factor (VEGF) exposure. In the first-line setting, VEGFR-2 inhibition with ramucirumab combined with platinum-based chemotherapy has achieved encouraging response rates and prolonged progression-free survival (PFS), though findings require cautious interpretation given small sample sizes and early termination of the trials without phase III confirmation. Multikinase inhibitors, such as sunitinib and lenvatinib, provide durable disease control in previously treated patients, with benefit closely linked to maintaining adequate dose intensity. Anti-angiogenic agents combined with immunotherapy have further expanded therapeutic options, particularly in anti-angiogenic-naïve patients; however, superiority over sequential use of these agents is unproven and additive toxicity is substantial. No validated predictive biomarkers currently guide treatment selection or sequencing. Anti-angiogenic therapy has emerged as a clinically active component of TC management across treatment lines and in rational combinations. The evidence base nevertheless rests on small phase II studies without confirmatory phase III data or broad regulatory approval. Future progress will depend on optimizing treatment sequencing, improving toxicity management, and advancing biomarker-driven patient selection through collaborative, multi-institutional efforts.
2026-08-23 | Thymic Carcinoma in a Patient with Lynch Syndrome
Presented at Mayo Clinic's 27th Annual Academic Excellence Day, April 2026, in Scottsdale, Arizona.
2026-08-13 | Precision Oncology in Thymic Epithelial Tumors: Therapeutic Horizons and Implementation Barriers.
Thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas, are rare, biologically heterogeneous thoracic malignancies with limited therapeutic advances since platinum-based regimens were adopted decades ago. Recent genomic and immunophenotypic profiling has uncovered recurrent genomic alterations and high programmed death-ligand 1 (PD-L1) expression, particularly in thymic carcinoma, yet few targeted or immunotherapies have achieved regulatory approval. This mini-review synthesizes current knowledge on TET heterogeneity and the genomic landscape, evaluates the clinical evidence supporting targeted agents and immune checkpoint inhibitors, and examines emerging biomarkers, including circulating tumor DNA. We also address practical barriers to precision oncology in TETs: challenges of next-generation sequencing implementation and cost in resource-limited settings; scarcity of large, biomarker-driven trials; and safety concerns unique to TETs (immune-related toxicity). Finally, we discuss the translational hurdles for antibody-drug conjugates and cellular therapies, limited validated cell surface targets, antigen heterogeneity, and preclinical model gaps and outline strategic paths forward to enable rational, safe, and equitable precision therapeutics for TET patients.
proteins
2025-12-10 | Circulating innate lymphoid cells and IL-18 as potential immune biomarkers in thymic tumors.
Thymic epithelial tumors (TETs) are rare malignancies frequently associated with autoimmunity. However, circulating immune biomarkers for patient stratification and disease monitoring remain undefined. Innate lymphoid cells (ILCs) are emerging regulators of tumor immunity, but their role in TETs has not yet been characterized. Peripheral blood samples from 32 patients with histologically confirmed TETs and 20 healthy donors were analyzed by multiparametric flow cytometry to quantify circulating ILC subsets. Serum cytokine concentrations were measured using multiplex immunoassays. Patients were stratified according to histology, disease activity, and presence of autoimmune manifestations. TETs displayed a significant expansion of circulating ILCs, mainly driven by an enrichment of ILC1, which was more pronounced in patients with active disease and in those with thymic carcinoma. Serum IL-18 levels were elevated-particularly in thymic carcinoma-and correlated with higher concentrations of type 2 cytokines (IL-4, IL-5, IL-9, IL-13). No concomitant increase in canonical ILC1 effector cytokines, including IFN-γ, was observed, indicating a functional dissociation between ILC1 expansion and their expected cytokine profile. These findings delineate a distinct systemic immune signature in TETs, characterized by IL-18 upregulation and altered ILC1 dynamics, with potential implications for immune regulation and autoimmunity. Circulating ILC profiling combined with IL-18 measurement may represent a promising approach for patient stratification, disease monitoring, and the development of novel immunomodulatory strategies in TETs.
2025-11-01 | 595 Preliminary results of safety and antitumor activity from a first-in-human phase 1 study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced tumors
2528 Background: Immune checkpoint inhibitors have transformed treatment landscape across multiple cancer types, however, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. In preclinical studies, the mouse surrogate of AWT020 demonstrated superior antitumor activity compared to anti-mPD-1 alone or in combination with IL-2. These findings suggest that AWT020 monotherapy may benefit patients resistant to anti-PD-1 therapies. Methods: This first-in-human Phase 1 dose escalation study evaluates AWT020 monotherapy in adults with advanced or metastatic cancers who failed or were intolerant to standard therapies. The dose-escalation utilizes a Bayesian Optimal Interval design. Key endpoints include safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor responses. Initial dose escalation results are presented herein. Clinical trial information: NCT06092580. Results: As of January 14, 2026, 41 patients received AWT020 at doses of 0.3, 0.6, and 1 mg/kg, including single-step (0.1 or 0.3 mg/kg) and two-step (0.1→0.3 mg/kg) priming regimens. Preliminary PK analysis showed approximately dose-proportional exposure. The majority of treatment-related adverse events (TRAEs) were low grade. The most frequently reported TRAEs were arthralgia (59%), rash (34%), fatigue (32%), and nausea (32%). Grade ≥3 TRAEs occurring in more than one subject included arthralgia (n=4), colitis (n=2), and thrombocytopenia (n=2). No patient experienced vascular leak syndrome. Among the 27 RECIST-evaluable patients, the overall response rate was 30%, and the disease control rate was 67%. Of the eight responders, five partial responders (thymic carcinoma, thymoma, clear cell renal cell carcinoma, neuroendocrine non-small cell lung cancer, and cholangiocarcinoma) had developed secondary resistance to anti-PD-(L)1 therapies. The remaining three responders were anti-PD-(L)1-naïve, including a cervical cancer patient who experienced confirmed complete response, and two partial responders with proficient mismatch repair (pMMR) tumors (adrenocortical carcinoma and uterine sarcoma). Ten additional patients with diverse cancer types achieved stable diseases, with tumor shrinkage observed in half of the patients, further supporting preliminary antitumor activity across broad tumor types. Conclusions: AWT020 demonstrates a manageable safety profile and promising early antitumor activity, including in patients with acquired resistance to anti-PD-(L)1 therapies and in patients with pMMR tumors which typically are unresponsive to immune monotherapy. Dose escalation is ongoing to establish MTD/RP2D. Clinical trial information: NCT06092580 .
2025-10-13 | Thymopentin Enhances Antitumor Immunity Through Thymic Rejuvenation and T Cell Functional Reprogramming
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment.
2025-05-28 | Combining SBRT with GM-CSF and peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors: A single arm, single center, phase II trial.
8110 Background: After the failure of first-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm single center, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 27 patients were enrolled in the trial from March 2021 to September 2024. One patient died of cardiac arrest before ORR evaluation during COVID-19 pandemic and was excluded, leaving 26 patients in the analysis, with 1 (3.8%) type A thymoma, 1 (3.8%) type AB thymoma,4 (15.4%) type B1 thymoma, 3 (11.5%) type B2 thymoma, 1 (3.8%) type B3 thymoma, 1 (3.8%) type B2+B3 thymoma, 13 (50.0%) thymic squamous cell carcinoma and 2 (7.7%) thymic neuroendocrine tumor. At a median follow-up of 26.4 months, 8 (30.8%) out of 26 patients had abscopal effects, and the ORR was 38.5%. The median OS for patients with abscopal effect has not been attained yet. The median PFS was 13.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 5 patients (19.2%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0). Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage IV thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .
2025-05-28 | First-in-human study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced cancer.
e14500 Background: Whileimmune checkpoint inhibitors have become the standard of care for multiple cancer types, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. Preclinical studies using a mouse surrogate have demonstrated superior antitumor activity compared to either anti-mPD-1 antibody alone or its combination with IL-2 in anti-PD-1 sensitive and resistant models. These findings suggest that AWT020 monotherapy has the potential to surpass standard anti-PD-1 therapies and provide a valuable treatment option for patients resistant to anti-PD-1 therapies. Methods: Study AWT020-001 (NCT06092580) is a first-in-human (FIH) trial evaluating AWT020 monotherapy (Q2W) in adults with advanced or metastatic cancers who have failed or were intolerant to standard therapies. The dose-escalation Phase 1 utilizes a Bayesian Optimal Interval design with a 28-day dose-limiting toxicity period. The primary objectives include assessing safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 (RP2D), and dosing interval. Secondary objectives include evaluating pharmacokinetics (PK), pharmacodynamic, immunogenicity, and antitumor response. Here, we present the initial results from the dose escalation phase. Results: As of January 8, 2025, 16 patients (8 males, 8 females) have been treated with AWT020 in three dose escalation groups (0.3, 0.6, and 1 mg/kg). Six patients received prior anti-PD-(L)1 therapies. Preliminary PK analysis indicates dose proportional properties of AWT020 within the 0.3 to 1 mg/kg dose range. Most treatment-related adverse events (TRAEs) were grades 1 to 2, including rash, arthralgia, hypothyroidism, nausea and fatigue. Grade ≥ 3 TRAEs included hypersensitivity reaction (Grade 4), hemoperitoneum, stomatitis, diabetes, worsening of rheumatoid arthritis, pain in extremity, and reactions related to infusion (cold sweat, arthralgia, backpain, chest pain, dysphonia, and dyspnoea). There was no evidence of vascular leak syndrome. Amongst the 12 patients with evaluable RECIST disease, two patients achieved partial response. One response occurred in a thymic carcinoma patient with primary resistance to anti-PD-1 therapy, and another was observed in a thymoma patient with acquired resistance to anti-PD-1 therapy. Six additional patients demonstrated disease stabilization, with three showing reductions in target lesions of 5%, 19% and 24%, further demonstrating antitumor activity. Conclusions: The initial data from this FIH study indicates that AWT020 has a manageable safety profile and is clinically active in cancers with primary or secondary resistance to anti-PD-1 therapies. The study is ongoing to optimize the dosing regimen and to establish MTD and RP2D. Clinical trial information: NCT06092580 .
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-04-03 | Abstract 3806: Development of a novel CAR T-cell therapy targeting thymic carcinoma
Abstract Introduction: Thymic carcinoma is a rare, highly aggressive mediastinal malignancy with limited effective therapies and considerable toxicity associated with immune checkpoint inhibitors. Although CAR T-cell therapy has revolutionized the treatment landscape for hematologic malignancies, its application to solid tumors, including thymic epithelial tumors, remains challenging due to disease rarity, a paucity of validated surface targets, and the risk of on-target, off-tumor autoimmune toxicity. In this study, we sought to address these barriers by characterizing antigen expression profiles across thymic carcinoma-relevant cell lines, engineering novel CAR constructs against prioritized candidate antigens, and evaluating antigen-specific cytotoxicity. These efforts aim to inform the development of next-generation cellular therapies tailored to the unique biology of this aggressive and understudied tumor type. Methods: Surface expression of TROP-2, c-KIT, and CD70 was quantified on candidate cell lines using flow cytometry. CAR T-cells were produced from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. CAR expression was confirmed by detection of Fab fragments on CD3+ T cells. Antigen-specific cytotoxicity was evaluated in vitro using co-culture assays with selected antigen-positive cell lines, and target cell killing was quantified by 7-AAD staining and flow cytometric analysis. Results: Flow cytometry demonstrated robust surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) across the T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction yielded CAR+ T cell populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three constructs exhibited potent antigen-specific cytotoxicity substantially exceeding GFP+ CD3+ control T cells, confirming selective recognition and killing of target cells. These findings provide some of the first in vitro evidence supporting TROP-2, c-KIT, and CD70 as viable immunotherapeutic targets for thymic carcinoma and demonstrate effective CAR expression and selective cytotoxicity. This work establishes a foundation for rational multi-antigen CAR T cell design in a historically understudied solid tumor. Ongoing studies include FACS-based CAR enrichment, characterization of exhaustion markers, development of a dual-antigen synNotch CAR to mitigate off-tumor toxicity, and in vivo validation in murine models to support future clinical translation. Citation Format: Layla Ahmadi, Malak Khalifeh, Dimitar Donovski, DuyKhanh Pham Ceppa, Patrick Loehrer, Rohan Maniar, Huda Salman. Development of a novel CAR T-cell therapy targeting thymic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3806.
2026-03-30 | Development of a Novel CAR T-Cell Therapy Targeting Thymic Carcinoma
Background Thymic carcinomas are rare anterior mediastinal malignancies with limited treatment options and modest responses to platinum-based chemotherapy. Immune checkpoint inhibitors have shown activity but often cause severe immune-related toxicities. Although CAR T-cell therapy has revolutionized hematologic cancer treatment, its application in thymic carcinoma is limited due to disease rarity, lack of tumor-specific surface antigens, and risks of on-target off-tumor toxicity, especially given the thymus’s role in immune tolerance. Recent studies have identified overexpression of TROP-2, c-KIT, and CD70 in thymic carcinoma, presenting novel therapeutic targets. Objectives Profile TROP-2, c-KIT, and CD70 surface expression on thymic carcinoma–relevant cell lines. Engineer CAR constructs targeting each antigen and validate CAR expression on T- cells. Evaluate antigen-specific cytotoxicity of CAR T-Cells in vitro to guide development of multi-antigen CAR T strategies. Methods Candidate cell lines were screened for surface expression of TROP-2, c-KIT, and CD70 using quantitative flow cytometry. CAR T-cells were generated from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. Antigen-specific cytotoxicity was evaluated through in vitro coculture assays using selected patient-derived cell lines. Cytotoxic effects were quantified by 7-AAD via flow cytometry. Results Flow cytometry confirmed high surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) in T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction produced Fab⁺ CAR-T populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three CAR-T constructs showed antigen-specific cytotoxicity significantly greater than GFP⁺ CD3⁺ controls. Conclusions This study provides early in vitro evidence supporting CAR T-cell therapy targeting TROP-2, c- KIT, and CD70 for thymic carcinoma. Results confirm strong CAR expression and potent, selective killing of antigen-positive targets.
2022-10-17 | Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.
2020-09-18 | Myasthenia Gravis Related to Thymic Carcinoma: A Case Study
Myasthenia gravis and thymoma are often presented in association with ∼10% of myasthenic cases having concomitant thymoma. Thymic carcinoma is one of the rarest/aggressive human epithelial tumors and has no correlation with myasthenia gravis hitherto. Here is provided a clinical case and review of literature on a very rare association of thymic carcinoma (with no sign of thymoma) and myasthenia gravis (antiacetylcholine receptor antibody positive). Two years after thymectomy, clinical evolution was satisfactory. This clinical case elicits hypothesis that thymic carcinoma may be related with myasthenia gravis, what may have good prognostic from oncologic and neurologic perspectives.
other
2025-06-11 | Case Report: Robust and durable response to the combination of tislelizumab and chemotherapy in advanced thymic epithelial tumors: a case series.
Thymic epithelial tumors (TETs), categorized predominantly as thymoma (T) or thymic carcinoma (TC), face a challenging prognosis and limited treatment options. Although chemotherapy remains the established treatment for advanced TETs, its responses tend to be short-lived. The emergence of immunotherapy, particularly programmed cell death-1 (PD-1) and programmed death ligand-1 inhibitors (PD-L1), is increasingly being regarded as a promising new treatment option for various malignancies. Herein, we present a case series of eight patients with TETs who received tislelizumab treatment at Jiangsu Provincial Hospital between 2021 and 2023. All cases were histologically confirmed as either thymoma or thymic carcinoma. Among these eight cases, six patients (5 thymic carcinomas [TC] and 1 thymoma [T]) received tislelizumab in combination with chemotherapy following multiple cycles of prior chemotherapy without achieving significant therapeutic response. Two TC patients were administered this combination regimen as first-line treatment. Following the initiation of immunotherapy, patients received tislelizumab at a dose of 200 mg every three weeks until disease progression or the occurrence of unacceptable toxicity. Treatment response was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. The 8 patients described had a median age of 59 years (range, 47-72). During the course of immunotherapy, five patients (62.5%) achieved partial response, and notably, even after transitioning to maintenance therapy with tislelizumab, the lesions continued to shrink, with the longest sustained partial response lasting over 2 years. Three patient (37.5%) experienced stable disease as their best response to immunotherapy. Among all these patients, three patients (37.5%) demonstrated initial efficacy but subsequently exhibited progressive disease (median progression-free survival of 14 months). All patients are still being followed up, with the longest PFS extending to 31 months. Notably, five of the eight patients underwent PD-L1 testing and were all found to be negative. Despite this, no immune-related Grade 3-5 adverse events (AEs) were reported and all AEs were manageable with supportive measures. Grade 1-2 AEs were adrenal insufficiency (n=1), thyroid dysfunction (n=1), and pneumonia (n=1). Our study findings suggest that the combination of immunotherapy and chemotherapy yields durable clinical responses in patients with TETs, suggesting its potential as a safe and effective first-line treatment strategy for advanced TETs. Notably, the therapeutic benefits of chemo-immunotherapy appear to extend beyond patients with high PD-L1 expression (≥50%), indicating that this treatment approach may not be strictly limited to individuals with elevated PD-L1 levels.
2024-09-26 | Characteristics of GTF2I L424H Mutated Thymoma and its Prognostic Impact: A Comprehensive Study
Thymic Epithelial Tumor (TET), a rare thoracic tumor, including thymoma and thymic carcinoma, has limited research on thymoma prognostic markers compared to thymic carcinoma. Using the cBiportal database, we analyzed gene expression, methylation, and mutation data in TETs. We explored the relationship between the GTF2I L424H mutation and thymoma pathology through differential gene expression, pathway enrichment analyses, and COX regression to develop a thymoma risk score. Compared with GTF2I wild-type, patients harboring GTF2I L424H mutation displayed distinctive gene expression and methylation profiles, resembling differences between pathology low-risk and high-risk patients. Importantly, patients with the GTF2I L424H mutation demonstrated a better prognosis than wild-type patients, but no such distinction was noted between low-risk and high-risk patients. Pathway analysis suggested that the mutation potentially regulates tumor development-related pathways, including the P53, Hippo, and TGFβ signaling pathways, ECM-receptor interaction, and tumor immune cell infiltration. Additionally, ten hub genes identified by cytoHubba, FGF20, FGF10, EGF, and TWIST1 were selected by stepwise multivariate Cox regression to construct a risk score model for thymoma. These findings highlight the potential role of the GTF2I L424H mutation as a prognostic factor, advocating for genetic profiling in personalized treatment strategies.
2024-05-01 | Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.
Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.
2023-10-31 | 1214 IL-12 vectors engineered to encode a functional p35-p40 heterodimer or a single p35 subunit for cancer immunotherapy
Background
Interleukin-12 (IL-12) is a 70-kDa heterodimeric cytokine composed of a 35 kDa(p35) and a 40 kDa subunit(p40). IL-12 has been proven to be a potent anticancer agent as it promotes the development of anti-tumor CD8+ T cells and NK cells. Although IL-12 has shown robust antitumor activity in preclinical studies and potent immune-stimulating potential in humans, there are no approved IL-12 therapeutic products due to its systemic toxicities. The IL-12 vectors described here are non-replicating MLV retrovectors which transduce rapidly dividing cells. Two types of IL-12 vectors were engineered. In the first type, both p35 and p40 are encoded for and linked by self-cleaving T2A peptide whereas in the second, only the p35 is encoded. The latter vector may be suitable for transducing tumor types that overexpress p40 such as squamous cell tumors.1 IL-12 tumor specificity can be achieved through local delivery of the vector, targeting via PiT2 receptors, the transduction and integration of rapidly dividing tumor cells, and/or pseudotyping the vector envelope to target tumor specific surface receptors.
Methods
All IL-12 genes were synthesized at Genscript and the final plasmids were confirmed by whole plasmid sequencing at Primordium Labs. Human A375 melanoma cells were transduced by the first IL-12 vector and subjected to Western blotting to confirm the protein expression of the two subunits. Both human and murine IL-12 as well as human p35 vectors were produced and tested. An mIL-12 expressing mouse colorectal CT26 stable cell line was established. P40 subunit vector was also separately engineered and used to generate A375-P40 overexpressing cells. Functional IL-12(p70) was tested by mIL-12 or hIL-12 ELISAs and in vitro assays.
Results
The IL-12 vector encoding for the two subunits can successfully transduce mouse and human cancer cells which then express and secrete biologically functional IL-12. The other vector encoding for p35 only, when transducing a p40 expressing cell line, produces and secretes a fully functional p70(IL-12) as well.
Conclusions
The data indicate the potential use of our IL-12 vectors as an efficient delivery system in IL-12 cancer gene therapy. Pre-clinical studies in a mouse tumor model of colorectal cancer demonstrate that IL-12 vector transduced tumors generate a significant immune response, inhibit tumor growth, and increase survival rate. Our current focus is the investigation of pseudotyped IL-12 vectors to target tumor specific surface receptors in in vivo tumor models.
Reference
Karlin, et al. J Cancer Metastasis Treat, 2022;8:15, Review: Thymic carcinoma: review and update.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
small molecules
2026-09-27 | Healing of Post-Operative Tracheal Disruption in a Patient with Thymic Carcinoma on Adjuvant Immunotherapy.
Pneumomediastinum from tracheal perforations due to primary repair breakdown can occur as a complication of thymic cancer surgery. Immunotherapy may be a viable adjuvant treatment for thymic carcinoma patients with tracheal perforations.
2026-09-20 | Advanced thymic epithelial tumours after neoadjuvant therapy: a narrative review of surgical challenges and strategies.
Thymic epithelial tumours, including thymoma and thymic carcinoma, are rare anterior mediastinal neoplasms. Complete surgical resection remains the strongest prognostic determinant, yet locally advanced disease frequently involves critical mediastinal structures and requires multimodality treatment. Neoadjuvant therapy is commonly used to improve resectability, although it alters operative anatomy in ways that can complicate subsequent surgery. This narrative review offers an updated appraisal of the surgical challenges that arise after neoadjuvant therapy, and of contemporary strategies for complex post-induction resection. A targeted literature search was carried out in PubMed, MEDLINE, Embase, Scopus, Web of Science and Google Scholar for English-language publications from January 1990 through January 2026. Search terms combined thymic malignancies, induction and chemoradiotherapy strategies, surgical resection, vascular reconstruction, pleural disease and survival. Emphasis was placed on contemporary literature (2010 to 2026) to reflect advances in imaging, multimodality therapy and surgical reconstruction. Neoadjuvant therapy produces dense fibrosis and obscures tissue planes, which complicates the dissection of critical structures. Imaging often underestimates stromal remodelling and residual viable tumour, so unexpected intraoperative difficulty is common. Vascular involvement is a major driver of operative complexity and frequently calls for resection and reconstruction, with contemporary graft patency of roughly 85% to 90% at five years in specialised series. In stage III disease, reported five-year survival after complete resection is approximately 70% to 90% for thymoma and 30% to 50% for thymic carcinoma. In stage IVa disease, cytoreductive surgery remains a treatment option when macroscopic complete resection is feasible, but the balance between aggressive procedures such as extrapleural pneumonectomy and more conservative pleurectomy/decortication must be weighed very carefully, since high-quality comparative evidence is lacking. Emerging data suggest that neoadjuvant chemoradiotherapy may yield higher R0 rates than chemotherapy alone, albeit at the cost of more pronounced fibrosis, although a matching survival benefit has not yet been proven. Molecular profiling (including GTF2I and TP53/KIT alterations) and AI-assisted imaging biomarkers are increasingly informing patient selection and surgical planning. Surgery after neoadjuvant therapy is feasible and safe in experienced centres, and in selected patients the oncologic outcomes appear to approach those of upfront resection with acceptable postoperative morbidity. Given the rarity of these tumours and the retrospective nature of most of the evidence, however, any comparison with upfront surgery should be interpreted with caution. Future progress will depend on international collaboration, prospective registries, validated molecular and imaging biomarkers, and standardisation of multimodality strategies.
2026-09-11 | Immune checkpoint inhibitors in thymic epithelial tumors: current evidence, immune-related toxicity, and perioperative considerations-a narrative review.
Thymic epithelial tumors (TETs) are rare mediastinal malignancies with unique immunobiological features related to thymic immune tolerance. Although immune checkpoint inhibitors (ICIs) have shown clinical activity, especially in thymic carcinoma, their use is limited by frequent and sometimes severe immune-related adverse events (irAEs), particularly in thymoma. This review summarizes current evidence on the efficacy, toxicity, biomarkers, and perioperative implications of ICIs in TETs. A narrative review was conducted using PubMed, Web of Science, and Embase for English-language studies on ICIs in TETs published from database inception to September 2025. Reference lists of relevant articles and guideline papers were also manually screened. Prospective trials, retrospective cohorts, guideline papers, and key mechanistic studies were prioritized, with emphasis on histology-specific efficacy, irAEs, biomarkers, and perioperative application. Current evidence suggests that ICIs have more consistent antitumor activity in thymic carcinoma than in thymoma. In contrast, thymoma carries a substantially higher risk of severe early irAEs, particularly myocarditis, myositis, and myasthenia gravis overlap syndromes. Biomarkers such as programmed death-ligand 1 (PD-L1) expression and immune-related signatures remain promising but are not yet sufficiently validated for routine patient selection. Perioperative immunotherapy is an emerging strategy, but current evidence remains limited and safety concerns are significant. ICIs represent a promising treatment option for selected patients with advanced TETs, particularly thymic carcinoma, but their clinical use remains restricted by toxicity and limited evidence. Future progress will depend on better risk stratification, biomarker-guided selection, and safer multidisciplinary integration.
2026-08-27 | Real-world outcomes of second-line therapy in advanced thymic carcinoma: a multicenter Turkish Oncology Group (TOG) study
Abstract Background Thymic carcinoma (TC) is a rare and aggressive malignancy with limited evidence guiding second-line treatment after prior systemic therapy. We evaluated real-world outcomes of second-line systemic therapy in a multicenter cohort. Methods Adults with unresectable, recurrent, or metastatic TC who received second-line systemic therapy after prior systemic therapy between 2010 and 2023 were retrospectively analyzed. Treatments were categorized as multidrug chemotherapy, gemcitabine monotherapy, PD-1 inhibitor therapy, or targeted therapy (sunitinib). For the primary comparison of multidrug chemotherapy versus gemcitabine monotherapy, propensity scores based on age, sex, ECOG performance status, Masaoka–Koga stage IV, prior surgery, and calendar year were used to generate overlap weights. Weighted Cox models used robust standard errors clustered by treatment center. A sensitivity propensity-score model additionally included first-line carboplatin–paclitaxel exposure (yes/no). Results A total of 107 patients from 20 treatment centers were included. Median age was 53.2 years (IQR, 41.5–58.0), 78 (72.9%) were male, 81 of 106 patients with available data (76.4%) had ECOG 0–1, and 61 (57.0%) had Masaoka–Koga stage IV disease at diagnosis. At a median follow-up of 35 months, median PFS and OS for the overall cohort were 13.6 and 35.0 months, respectively. In the primary overlap-weighted comparison ( n = 89), multidrug chemotherapy was associated with a lower hazard of progression or death than gemcitabine monotherapy (HR, 0.29; 95% CI, 0.14–0.59; p < 0.001) and a lower hazard of death (HR, 0.42; 95% CI, 0.18–0.97; p = 0.043). In a sensitivity model additionally incorporating first-line carboplatin–paclitaxel exposure, the PFS estimate remained significant (HR, 0.32; 95% CI, 0.16–0.65; p = 0.0015), whereas the OS estimate remained directionally similar but was less precise (HR, 0.46; 95% CI, 0.19–1.11; p = 0.083). The PD-1 inhibitor group ( n = 13) had median PFS and OS of 15.0 and 48.0 months, respectively, in unadjusted descriptive analyses. Conclusions In this retrospective cohort, multidrug chemotherapy was associated with lower hazards of progression or death and of death than gemcitabine monotherapy in the primary overlap-weighted analysis. A sensitivity analysis additionally accounting for first-line carboplatin–paclitaxel exposure preserved the PFS association and yielded a similar but less precise OS estimate. Outcomes observed with PD-1 inhibitors were favorable but should be interpreted descriptively because of the small sample size, later treatment era, and potential residual confounding. These findings are hypothesis-generating and require prospective validation.
2026-08-27 | Robotic-Assisted Extended Thymus Carcinoma Resection With Unilateral Total Pleurectomy and Hyperthermic Intrathoracic Chemotherapy (HITOC).
Thymic squamous cell carcinoma (SCC) is an aggressive form of thymic cancer that is often diagnosed at an advanced stage. Hyperthermic intrathoracic chemotherapy (HITOC) is a treatment option for advanced thoracic and especially pleural malignancies, though it is not yet the standard of care. However, the success of treating pleural cancers with HITOC protocols has been well documented in selected cases. Robotic-assisted thoracoscopic surgery (RATS) has become the standard procedure for thymectomy, even for locally advanced tumors. In this report, we describe the treatment of a 53-year-old patient with a locally advanced Masaoka-Koga stage IVa thymic SCC and concomitant limited pleural carcinomatosis who was successfully treated by RATS thymectomy and HITOC. The report highlights the diagnostic challenges, therapeutic approach, and postoperative care, emphasizing the advantages of minimally invasive, robot-assisted surgery even in advanced cases. RATS with HITOC can be a safe and effective method for the treatment of advanced thymic carcinoma. This case report demonstrates that this procedure enables rapid postoperative recovery and can be performed with minimal morbidity.
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2026-09-30 | A Case Report of Bilateral Thyroid Thymic Carcinoma with Multiple Cervical Lymph Node Metastases: Clinical Manifestations and Imaging Characteristics.
Intrathyroidal thymic carcinoma (ITTC) is a rare low-grade malignant tumor arising within the thyroid gland. It exhibits histological and immunophenotypic features similar to thymic carcinoma. Due to its rarity and non-specific imaging findings, preoperative diagnosis remains challenging. We report a case of a 60-year-old male who presented with hoarseness and dysphagia. Ultrasound revealed multiple bilateral thyroid nodules with irregular margins and heterogeneous internal echoes, along with bilateral cervical lymphadenopathy. Enhanced CT showed heterogeneous enhancement of the thyroid and enlarged lymph nodes. The patient underwent extended radical resection of bilateral thyroid cancer with mediastinal lymph node dissection. Postoperative pathology and immunohistochemistry confirmed the diagnosis of bilateral thyroid thymic carcinoma with multiple cervical lymph node metastases. ITTC should be considered in the differential diagnosis of thyroid nodules with suspicious ultrasound features, especially when associated with cervical lymph node metastases. Positive expression of CD5 and CD117 with negative expression of Tg and TTF-1 is diagnostic. Treatment follows principles similar to those for thymic carcinoma, and complete surgical resection remains the mainstay.
2026-09-23 | Ivonescimab plus chemotherapy as first-line treatment for advanced thymic carcinoma: preliminary results of a phase II trial with biomarker analyses.
Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4+/CD8+ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4+/CD8+ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4+/CD8+ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.
2026-09-20 | Anti-angiogenic therapy in thymic carcinoma: a narrative review of current evidence and emerging combinations.
Thymic carcinoma (TC) is a rare and aggressive malignancy with limited systemic treatment options. Although platinum-based chemotherapy has historically been the first-line standard, anti-angiogenic therapy has emerged as an important therapeutic strategy across treatment settings. This review synthesizes current evidence on anti-angiogenic therapies, as monotherapy and in combination with chemotherapy or immunotherapy, and defines their evolving role in TC management. A targeted narrative review was conducted using PubMed/MEDLINE, Embase, Google Scholar, ClinicalTrials.gov, conference proceedings, and reference list screening to identify clinical studies of anti-angiogenic therapy in TC published from January 2000 to January 2026. Anti-angiogenic therapy demonstrates clinical activity across treatment settings in TC. Yet the magnitude and durability of benefit vary by agent, treatment line, and prior vascular endothelial growth factor (VEGF) exposure. In the first-line setting, VEGFR-2 inhibition with ramucirumab combined with platinum-based chemotherapy has achieved encouraging response rates and prolonged progression-free survival (PFS), though findings require cautious interpretation given small sample sizes and early termination of the trials without phase III confirmation. Multikinase inhibitors, such as sunitinib and lenvatinib, provide durable disease control in previously treated patients, with benefit closely linked to maintaining adequate dose intensity. Anti-angiogenic agents combined with immunotherapy have further expanded therapeutic options, particularly in anti-angiogenic-naïve patients; however, superiority over sequential use of these agents is unproven and additive toxicity is substantial. No validated predictive biomarkers currently guide treatment selection or sequencing. Anti-angiogenic therapy has emerged as a clinically active component of TC management across treatment lines and in rational combinations. The evidence base nevertheless rests on small phase II studies without confirmatory phase III data or broad regulatory approval. Future progress will depend on optimizing treatment sequencing, improving toxicity management, and advancing biomarker-driven patient selection through collaborative, multi-institutional efforts.
2026-08-23 | Thymic Carcinoma in a Patient with Lynch Syndrome
Presented at Mayo Clinic's 27th Annual Academic Excellence Day, April 2026, in Scottsdale, Arizona.
2026-08-13 | Precision Oncology in Thymic Epithelial Tumors: Therapeutic Horizons and Implementation Barriers.
Thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas, are rare, biologically heterogeneous thoracic malignancies with limited therapeutic advances since platinum-based regimens were adopted decades ago. Recent genomic and immunophenotypic profiling has uncovered recurrent genomic alterations and high programmed death-ligand 1 (PD-L1) expression, particularly in thymic carcinoma, yet few targeted or immunotherapies have achieved regulatory approval. This mini-review synthesizes current knowledge on TET heterogeneity and the genomic landscape, evaluates the clinical evidence supporting targeted agents and immune checkpoint inhibitors, and examines emerging biomarkers, including circulating tumor DNA. We also address practical barriers to precision oncology in TETs: challenges of next-generation sequencing implementation and cost in resource-limited settings; scarcity of large, biomarker-driven trials; and safety concerns unique to TETs (immune-related toxicity). Finally, we discuss the translational hurdles for antibody-drug conjugates and cellular therapies, limited validated cell surface targets, antigen heterogeneity, and preclinical model gaps and outline strategic paths forward to enable rational, safe, and equitable precision therapeutics for TET patients.
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2025-12-10 | Circulating innate lymphoid cells and IL-18 as potential immune biomarkers in thymic tumors.
Thymic epithelial tumors (TETs) are rare malignancies frequently associated with autoimmunity. However, circulating immune biomarkers for patient stratification and disease monitoring remain undefined. Innate lymphoid cells (ILCs) are emerging regulators of tumor immunity, but their role in TETs has not yet been characterized. Peripheral blood samples from 32 patients with histologically confirmed TETs and 20 healthy donors were analyzed by multiparametric flow cytometry to quantify circulating ILC subsets. Serum cytokine concentrations were measured using multiplex immunoassays. Patients were stratified according to histology, disease activity, and presence of autoimmune manifestations. TETs displayed a significant expansion of circulating ILCs, mainly driven by an enrichment of ILC1, which was more pronounced in patients with active disease and in those with thymic carcinoma. Serum IL-18 levels were elevated-particularly in thymic carcinoma-and correlated with higher concentrations of type 2 cytokines (IL-4, IL-5, IL-9, IL-13). No concomitant increase in canonical ILC1 effector cytokines, including IFN-γ, was observed, indicating a functional dissociation between ILC1 expansion and their expected cytokine profile. These findings delineate a distinct systemic immune signature in TETs, characterized by IL-18 upregulation and altered ILC1 dynamics, with potential implications for immune regulation and autoimmunity. Circulating ILC profiling combined with IL-18 measurement may represent a promising approach for patient stratification, disease monitoring, and the development of novel immunomodulatory strategies in TETs.
2025-11-01 | 595 Preliminary results of safety and antitumor activity from a first-in-human phase 1 study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced tumors
2528 Background: Immune checkpoint inhibitors have transformed treatment landscape across multiple cancer types, however, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. In preclinical studies, the mouse surrogate of AWT020 demonstrated superior antitumor activity compared to anti-mPD-1 alone or in combination with IL-2. These findings suggest that AWT020 monotherapy may benefit patients resistant to anti-PD-1 therapies. Methods: This first-in-human Phase 1 dose escalation study evaluates AWT020 monotherapy in adults with advanced or metastatic cancers who failed or were intolerant to standard therapies. The dose-escalation utilizes a Bayesian Optimal Interval design. Key endpoints include safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor responses. Initial dose escalation results are presented herein. Clinical trial information: NCT06092580. Results: As of January 14, 2026, 41 patients received AWT020 at doses of 0.3, 0.6, and 1 mg/kg, including single-step (0.1 or 0.3 mg/kg) and two-step (0.1→0.3 mg/kg) priming regimens. Preliminary PK analysis showed approximately dose-proportional exposure. The majority of treatment-related adverse events (TRAEs) were low grade. The most frequently reported TRAEs were arthralgia (59%), rash (34%), fatigue (32%), and nausea (32%). Grade ≥3 TRAEs occurring in more than one subject included arthralgia (n=4), colitis (n=2), and thrombocytopenia (n=2). No patient experienced vascular leak syndrome. Among the 27 RECIST-evaluable patients, the overall response rate was 30%, and the disease control rate was 67%. Of the eight responders, five partial responders (thymic carcinoma, thymoma, clear cell renal cell carcinoma, neuroendocrine non-small cell lung cancer, and cholangiocarcinoma) had developed secondary resistance to anti-PD-(L)1 therapies. The remaining three responders were anti-PD-(L)1-naïve, including a cervical cancer patient who experienced confirmed complete response, and two partial responders with proficient mismatch repair (pMMR) tumors (adrenocortical carcinoma and uterine sarcoma). Ten additional patients with diverse cancer types achieved stable diseases, with tumor shrinkage observed in half of the patients, further supporting preliminary antitumor activity across broad tumor types. Conclusions: AWT020 demonstrates a manageable safety profile and promising early antitumor activity, including in patients with acquired resistance to anti-PD-(L)1 therapies and in patients with pMMR tumors which typically are unresponsive to immune monotherapy. Dose escalation is ongoing to establish MTD/RP2D. Clinical trial information: NCT06092580 .
2025-10-13 | Thymopentin Enhances Antitumor Immunity Through Thymic Rejuvenation and T Cell Functional Reprogramming
Background/Objectives: T cell dysfunction represents a fundamental barrier to effective cancer immunotherapy. Although immune checkpoint blockades and adoptive cell transfer have achieved clinical success, therapeutic resistance remains prevalent across cancer types. Thymopentin (TP5), a synthetic immunomodulatory pentapeptide (Arg-Lys-Asp-Val-Tyr), has demonstrated immunostimulatory properties, yet its anticancer potential remains unexplored. The aim of this study was to investigate TP5’s antitumor efficacy and underlying immunological mechanisms. Methods: We evaluated TP5’s therapeutic effects in multiple murine tumor models, including B16-F10 melanoma, MC38 colorectal carcinoma, Hepa 1-6, and LM3 hepatocellular carcinoma. Immune cell populations and functional states were characterized using flow cytometry, ELISAs, and immunofluorescence analyses. The potential of TP5 as an adjuvant for T cell-based therapies was also systematically assessed. Results: The TP5 treatment markedly suppressed tumor growth across caner models through strictly T cell-dependent mechanisms. Critically, TP5 promoted thymic rejuvenation under immunocompromised conditions, restoring the thymus–tumor immunological balance and revitalizing peripheral T cell immunity. TP5 functionally reprogrammed T cell states, preserving effector function while ameliorating exhaustion. Furthermore, TP5 demonstrated synergistic efficacy when combined with adoptive T cell therapies, enhancing both proliferation and effector functions. Conclusions: TP5 represents a promising immunomodulator that addresses fundamental limitations of current T cell therapies by simultaneously enhancing T cell function and reversing thymic involution under immunocompromised conditions. Our findings provide compelling evidence for TP5’s clinical translation in cancer treatment.
2025-05-28 | Combining SBRT with GM-CSF and peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors: A single arm, single center, phase II trial.
8110 Background: After the failure of first-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm single center, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 27 patients were enrolled in the trial from March 2021 to September 2024. One patient died of cardiac arrest before ORR evaluation during COVID-19 pandemic and was excluded, leaving 26 patients in the analysis, with 1 (3.8%) type A thymoma, 1 (3.8%) type AB thymoma,4 (15.4%) type B1 thymoma, 3 (11.5%) type B2 thymoma, 1 (3.8%) type B3 thymoma, 1 (3.8%) type B2+B3 thymoma, 13 (50.0%) thymic squamous cell carcinoma and 2 (7.7%) thymic neuroendocrine tumor. At a median follow-up of 26.4 months, 8 (30.8%) out of 26 patients had abscopal effects, and the ORR was 38.5%. The median OS for patients with abscopal effect has not been attained yet. The median PFS was 13.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 5 patients (19.2%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0). Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage IV thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .
2025-05-28 | First-in-human study of AWT020, a bifunctional anti-PD-1/IL-2 fusion protein, in patients with advanced cancer.
e14500 Background: Whileimmune checkpoint inhibitors have become the standard of care for multiple cancer types, resistance to anti-PD-(L)1 therapies remains a significant unmet medical need. AWT020 is a bifunctional fusion protein comprised of an anti-PD-1 antibody and a potency optimized IL-2. Preclinical studies using a mouse surrogate have demonstrated superior antitumor activity compared to either anti-mPD-1 antibody alone or its combination with IL-2 in anti-PD-1 sensitive and resistant models. These findings suggest that AWT020 monotherapy has the potential to surpass standard anti-PD-1 therapies and provide a valuable treatment option for patients resistant to anti-PD-1 therapies. Methods: Study AWT020-001 (NCT06092580) is a first-in-human (FIH) trial evaluating AWT020 monotherapy (Q2W) in adults with advanced or metastatic cancers who have failed or were intolerant to standard therapies. The dose-escalation Phase 1 utilizes a Bayesian Optimal Interval design with a 28-day dose-limiting toxicity period. The primary objectives include assessing safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 (RP2D), and dosing interval. Secondary objectives include evaluating pharmacokinetics (PK), pharmacodynamic, immunogenicity, and antitumor response. Here, we present the initial results from the dose escalation phase. Results: As of January 8, 2025, 16 patients (8 males, 8 females) have been treated with AWT020 in three dose escalation groups (0.3, 0.6, and 1 mg/kg). Six patients received prior anti-PD-(L)1 therapies. Preliminary PK analysis indicates dose proportional properties of AWT020 within the 0.3 to 1 mg/kg dose range. Most treatment-related adverse events (TRAEs) were grades 1 to 2, including rash, arthralgia, hypothyroidism, nausea and fatigue. Grade ≥ 3 TRAEs included hypersensitivity reaction (Grade 4), hemoperitoneum, stomatitis, diabetes, worsening of rheumatoid arthritis, pain in extremity, and reactions related to infusion (cold sweat, arthralgia, backpain, chest pain, dysphonia, and dyspnoea). There was no evidence of vascular leak syndrome. Amongst the 12 patients with evaluable RECIST disease, two patients achieved partial response. One response occurred in a thymic carcinoma patient with primary resistance to anti-PD-1 therapy, and another was observed in a thymoma patient with acquired resistance to anti-PD-1 therapy. Six additional patients demonstrated disease stabilization, with three showing reductions in target lesions of 5%, 19% and 24%, further demonstrating antitumor activity. Conclusions: The initial data from this FIH study indicates that AWT020 has a manageable safety profile and is clinically active in cancers with primary or secondary resistance to anti-PD-1 therapies. The study is ongoing to optimize the dosing regimen and to establish MTD and RP2D. Clinical trial information: NCT06092580 .
cell therapies
2026-04-21 | Left brachiocephalic vein replacement and superior vena cava reconstruction with aortic homograft for thymic carcinoma.
Advanced intrathoracic tumours pose a significant challenge for thoracic surgeons because of the possible involvement of adjacent vital organs and major mediastinal vessels. The most effective therapeutic option for resectable thymic carcinomas is currently represented by complete surgical asportation en bloc with adjacent infiltrated structures to achieve more effective oncological outcomes. Vascular reconstruction, when required, is traditionally performed using prosthetic conduits; however, vascular homografts represent a potential alternative with several surgical and clinical advantages. We report a case of a large thymic carcinoma with mediastinal vessel invasion successfully treated by surgical resection and vascular reconstruction using an aortic homograft.
2026-04-03 | Abstract 3806: Development of a novel CAR T-cell therapy targeting thymic carcinoma
Abstract Introduction: Thymic carcinoma is a rare, highly aggressive mediastinal malignancy with limited effective therapies and considerable toxicity associated with immune checkpoint inhibitors. Although CAR T-cell therapy has revolutionized the treatment landscape for hematologic malignancies, its application to solid tumors, including thymic epithelial tumors, remains challenging due to disease rarity, a paucity of validated surface targets, and the risk of on-target, off-tumor autoimmune toxicity. In this study, we sought to address these barriers by characterizing antigen expression profiles across thymic carcinoma-relevant cell lines, engineering novel CAR constructs against prioritized candidate antigens, and evaluating antigen-specific cytotoxicity. These efforts aim to inform the development of next-generation cellular therapies tailored to the unique biology of this aggressive and understudied tumor type. Methods: Surface expression of TROP-2, c-KIT, and CD70 was quantified on candidate cell lines using flow cytometry. CAR T-cells were produced from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. CAR expression was confirmed by detection of Fab fragments on CD3+ T cells. Antigen-specific cytotoxicity was evaluated in vitro using co-culture assays with selected antigen-positive cell lines, and target cell killing was quantified by 7-AAD staining and flow cytometric analysis. Results: Flow cytometry demonstrated robust surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) across the T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction yielded CAR+ T cell populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three constructs exhibited potent antigen-specific cytotoxicity substantially exceeding GFP+ CD3+ control T cells, confirming selective recognition and killing of target cells. These findings provide some of the first in vitro evidence supporting TROP-2, c-KIT, and CD70 as viable immunotherapeutic targets for thymic carcinoma and demonstrate effective CAR expression and selective cytotoxicity. This work establishes a foundation for rational multi-antigen CAR T cell design in a historically understudied solid tumor. Ongoing studies include FACS-based CAR enrichment, characterization of exhaustion markers, development of a dual-antigen synNotch CAR to mitigate off-tumor toxicity, and in vivo validation in murine models to support future clinical translation. Citation Format: Layla Ahmadi, Malak Khalifeh, Dimitar Donovski, DuyKhanh Pham Ceppa, Patrick Loehrer, Rohan Maniar, Huda Salman. Development of a novel CAR T-cell therapy targeting thymic carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3806.
2026-03-30 | Development of a Novel CAR T-Cell Therapy Targeting Thymic Carcinoma
Background Thymic carcinomas are rare anterior mediastinal malignancies with limited treatment options and modest responses to platinum-based chemotherapy. Immune checkpoint inhibitors have shown activity but often cause severe immune-related toxicities. Although CAR T-cell therapy has revolutionized hematologic cancer treatment, its application in thymic carcinoma is limited due to disease rarity, lack of tumor-specific surface antigens, and risks of on-target off-tumor toxicity, especially given the thymus’s role in immune tolerance. Recent studies have identified overexpression of TROP-2, c-KIT, and CD70 in thymic carcinoma, presenting novel therapeutic targets. Objectives Profile TROP-2, c-KIT, and CD70 surface expression on thymic carcinoma–relevant cell lines. Engineer CAR constructs targeting each antigen and validate CAR expression on T- cells. Evaluate antigen-specific cytotoxicity of CAR T-Cells in vitro to guide development of multi-antigen CAR T strategies. Methods Candidate cell lines were screened for surface expression of TROP-2, c-KIT, and CD70 using quantitative flow cytometry. CAR T-cells were generated from healthy donor PBMCs via lentiviral transduction and expanded ex vivo. Antigen-specific cytotoxicity was evaluated through in vitro coculture assays using selected patient-derived cell lines. Cytotoxic effects were quantified by 7-AAD via flow cytometry. Results Flow cytometry confirmed high surface expression of TROP-2 (83%), c-KIT (88%), and CD70 (99%) in T1889, Kasumi, and U266 cell lines, respectively. Lentiviral transduction produced Fab⁺ CAR-T populations of 48.2% (TROP-2), 24.7% (c-KIT), and 47.5% (CD70). All three CAR-T constructs showed antigen-specific cytotoxicity significantly greater than GFP⁺ CD3⁺ controls. Conclusions This study provides early in vitro evidence supporting CAR T-cell therapy targeting TROP-2, c- KIT, and CD70 for thymic carcinoma. Results confirm strong CAR expression and potent, selective killing of antigen-positive targets.
2022-10-17 | Upper thoracic empyema and concomitant superior vena cava syndrome treated with reconstructive surgery using a pedicled omental flap.
Superior vena cava (SVC) syndrome refers to a constellation of symptoms secondary to obstruction of blood flow through the SVC. In this condition, venous blood that usually drains into the SVC is diverted into the inferior vena cava (IVC) via collateral veins. Reconstructive surgery is challenging in such cases owing to the anomalous venous system. In this case report, we describe reconstructive surgery using a pedicled omental flap in a patient with upper thoracic empyema and concomitant SVC syndrome. A 68-year-old man underwent resection of malignant thymoma, the bilateral brachiocephalic veins, and a part of the right upper lobe, followed by polytetrafluoroethylene (PTFE) graft placement for venous system reconstruction, 2 years prior to presentation. He developed postoperative upper thoracic cavity empyema, which necessitated PTFE graft removal. Although the infection was controlled after 2 months, multiple right upper lobe pulmonary fistulas persisted, and the patient was referred to our department for further evaluation. Contrast-enhanced computed tomography revealed SVC syndrome characterized by SVC obstruction and consequent drainage of venous blood from the upper trunk into the IVC via collateral vessels. We debrided necrotic and infected tissues, and a pedicled omental flap was placed for upper lobe fistula coverage. The patient showed an uncomplicated postoperative course, and no recurrent empyema or pulmonary fistulas were observed 3 years postoperatively. Flaps associated with the SVC system show high venous pressures. The use of a pedicled omental flap was deemed feasible because this graft reaches the upper thorax even though it is associated with the IVC system.
2020-09-18 | Myasthenia Gravis Related to Thymic Carcinoma: A Case Study
Myasthenia gravis and thymoma are often presented in association with ∼10% of myasthenic cases having concomitant thymoma. Thymic carcinoma is one of the rarest/aggressive human epithelial tumors and has no correlation with myasthenia gravis hitherto. Here is provided a clinical case and review of literature on a very rare association of thymic carcinoma (with no sign of thymoma) and myasthenia gravis (antiacetylcholine receptor antibody positive). Two years after thymectomy, clinical evolution was satisfactory. This clinical case elicits hypothesis that thymic carcinoma may be related with myasthenia gravis, what may have good prognostic from oncologic and neurologic perspectives.
other
2025-06-11 | Case Report: Robust and durable response to the combination of tislelizumab and chemotherapy in advanced thymic epithelial tumors: a case series.
Thymic epithelial tumors (TETs), categorized predominantly as thymoma (T) or thymic carcinoma (TC), face a challenging prognosis and limited treatment options. Although chemotherapy remains the established treatment for advanced TETs, its responses tend to be short-lived. The emergence of immunotherapy, particularly programmed cell death-1 (PD-1) and programmed death ligand-1 inhibitors (PD-L1), is increasingly being regarded as a promising new treatment option for various malignancies. Herein, we present a case series of eight patients with TETs who received tislelizumab treatment at Jiangsu Provincial Hospital between 2021 and 2023. All cases were histologically confirmed as either thymoma or thymic carcinoma. Among these eight cases, six patients (5 thymic carcinomas [TC] and 1 thymoma [T]) received tislelizumab in combination with chemotherapy following multiple cycles of prior chemotherapy without achieving significant therapeutic response. Two TC patients were administered this combination regimen as first-line treatment. Following the initiation of immunotherapy, patients received tislelizumab at a dose of 200 mg every three weeks until disease progression or the occurrence of unacceptable toxicity. Treatment response was assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. The 8 patients described had a median age of 59 years (range, 47-72). During the course of immunotherapy, five patients (62.5%) achieved partial response, and notably, even after transitioning to maintenance therapy with tislelizumab, the lesions continued to shrink, with the longest sustained partial response lasting over 2 years. Three patient (37.5%) experienced stable disease as their best response to immunotherapy. Among all these patients, three patients (37.5%) demonstrated initial efficacy but subsequently exhibited progressive disease (median progression-free survival of 14 months). All patients are still being followed up, with the longest PFS extending to 31 months. Notably, five of the eight patients underwent PD-L1 testing and were all found to be negative. Despite this, no immune-related Grade 3-5 adverse events (AEs) were reported and all AEs were manageable with supportive measures. Grade 1-2 AEs were adrenal insufficiency (n=1), thyroid dysfunction (n=1), and pneumonia (n=1). Our study findings suggest that the combination of immunotherapy and chemotherapy yields durable clinical responses in patients with TETs, suggesting its potential as a safe and effective first-line treatment strategy for advanced TETs. Notably, the therapeutic benefits of chemo-immunotherapy appear to extend beyond patients with high PD-L1 expression (≥50%), indicating that this treatment approach may not be strictly limited to individuals with elevated PD-L1 levels.
2024-09-26 | Characteristics of GTF2I L424H Mutated Thymoma and its Prognostic Impact: A Comprehensive Study
Thymic Epithelial Tumor (TET), a rare thoracic tumor, including thymoma and thymic carcinoma, has limited research on thymoma prognostic markers compared to thymic carcinoma. Using the cBiportal database, we analyzed gene expression, methylation, and mutation data in TETs. We explored the relationship between the GTF2I L424H mutation and thymoma pathology through differential gene expression, pathway enrichment analyses, and COX regression to develop a thymoma risk score. Compared with GTF2I wild-type, patients harboring GTF2I L424H mutation displayed distinctive gene expression and methylation profiles, resembling differences between pathology low-risk and high-risk patients. Importantly, patients with the GTF2I L424H mutation demonstrated a better prognosis than wild-type patients, but no such distinction was noted between low-risk and high-risk patients. Pathway analysis suggested that the mutation potentially regulates tumor development-related pathways, including the P53, Hippo, and TGFβ signaling pathways, ECM-receptor interaction, and tumor immune cell infiltration. Additionally, ten hub genes identified by cytoHubba, FGF20, FGF10, EGF, and TWIST1 were selected by stepwise multivariate Cox regression to construct a risk score model for thymoma. These findings highlight the potential role of the GTF2I L424H mutation as a prognostic factor, advocating for genetic profiling in personalized treatment strategies.
2024-05-01 | Long non-coding RNA LOXL1-AS1: a potential biomarker and therapeutic target in human malignant tumors.
Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified their important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1), a newly discovered lncRNA located on human chromosome 15q24.1, has recently been shown to be involved in the occurrence and progression of various malignancies, such as colorectal cancer, gastric cancer, hepatocellular carcinoma, prostate cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, breast cancer, glioma, thymic carcinoma, pancreatic carcinoma. LOXL1-AS1 acts as competitive endogenous RNA (ceRNA) and via sponging various miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p and miR-1224-5p to promote tumor cell proliferation, invasion, migration, apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT). In addition, LOXL1-AS1 is involved in the regulation of P13K/AKT and MAPK signaling pathways. This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.
2023-10-31 | 1214 IL-12 vectors engineered to encode a functional p35-p40 heterodimer or a single p35 subunit for cancer immunotherapy
Background
Interleukin-12 (IL-12) is a 70-kDa heterodimeric cytokine composed of a 35 kDa(p35) and a 40 kDa subunit(p40). IL-12 has been proven to be a potent anticancer agent as it promotes the development of anti-tumor CD8+ T cells and NK cells. Although IL-12 has shown robust antitumor activity in preclinical studies and potent immune-stimulating potential in humans, there are no approved IL-12 therapeutic products due to its systemic toxicities. The IL-12 vectors described here are non-replicating MLV retrovectors which transduce rapidly dividing cells. Two types of IL-12 vectors were engineered. In the first type, both p35 and p40 are encoded for and linked by self-cleaving T2A peptide whereas in the second, only the p35 is encoded. The latter vector may be suitable for transducing tumor types that overexpress p40 such as squamous cell tumors.1 IL-12 tumor specificity can be achieved through local delivery of the vector, targeting via PiT2 receptors, the transduction and integration of rapidly dividing tumor cells, and/or pseudotyping the vector envelope to target tumor specific surface receptors.
Methods
All IL-12 genes were synthesized at Genscript and the final plasmids were confirmed by whole plasmid sequencing at Primordium Labs. Human A375 melanoma cells were transduced by the first IL-12 vector and subjected to Western blotting to confirm the protein expression of the two subunits. Both human and murine IL-12 as well as human p35 vectors were produced and tested. An mIL-12 expressing mouse colorectal CT26 stable cell line was established. P40 subunit vector was also separately engineered and used to generate A375-P40 overexpressing cells. Functional IL-12(p70) was tested by mIL-12 or hIL-12 ELISAs and in vitro assays.
Results
The IL-12 vector encoding for the two subunits can successfully transduce mouse and human cancer cells which then express and secrete biologically functional IL-12. The other vector encoding for p35 only, when transducing a p40 expressing cell line, produces and secretes a fully functional p70(IL-12) as well.
Conclusions
The data indicate the potential use of our IL-12 vectors as an efficient delivery system in IL-12 cancer gene therapy. Pre-clinical studies in a mouse tumor model of colorectal cancer demonstrate that IL-12 vector transduced tumors generate a significant immune response, inhibit tumor growth, and increase survival rate. Our current focus is the investigation of pseudotyped IL-12 vectors to target tumor specific surface receptors in in vivo tumor models.
Reference
Karlin, et al. J Cancer Metastasis Treat, 2022;8:15, Review: Thymic carcinoma: review and update.
2022-04-22 | Long Non-Coding RNAs in the Cell Fate Determination of Neoplastic Thymic Epithelial Cells
Thymic Epithelial Tumors (TETs) arise from epithelial cells of the thymus and are very rare neoplasms comprising Thymoma, Thymic carcinoma, and Thymic Neuroendocrine tumors that still require in-depth molecular characterization. Long non-coding RNAs (lncRNAs) are emerging as relevant gene expression modulators involved in the deregulation of several networks in almost all types of human cancer, including TETs. LncRNAs act at different control levels in the regulation of gene expression, from transcription to translation, and modulate several pathways relevant to cell fate determination under normal and pathological conditions. The activity of lncRNAs is strongly dependent on their expression, localization, and post-transcriptional modifications. Starting from our recently published studies, this review focuses on the involvement of lncRNAs in the acquisition of malignant traits by neoplastic thymic epithelial cells, and describes the possible use of these molecules as targets for the design of novel therapeutic approaches specific for TET. Furthermore, the involvement of lncRNAs in myasthenia gravis (MG)-related thymoma, which is still under investigation, is discussed.
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Drug Discovery Landscape
1 orphan drug designation for Thymic carcinoma.
1 orphan drug designation for Thymic carcinoma.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
(1R,2R)-1,2-cyclohexane-diaminepyrophosphato-platinum(II) | small molecules | FDA | Promontory Therapeutics, Inc. |
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