RARE DISEASE
Malignant germ cell tumor of ovary
Malignant germ cell tumor of ovary
Malignant germ cell tumor of ovary
Synonyms: MOGCT, Malignant ovarian germ cell tumor, Ovarian germ cell cancer
Synonyms: MOGCT, Malignant ovarian germ cell tumor, Ovarian germ cell cancer
Synonyms: MOGCT, Malignant ovarian germ cell tumor, Ovarian germ cell cancer
Drug discovery
1
drug
With orphan designation
Overview
Malignant germ cell tumors of the ovary are rare, aggressive cancers arising from primordial germ cells, accounting for 2.6% of ovarian malignancies [1][3][12]. They predominantly affect adolescents and young women, presenting with pelvic masses, abdominal pain, or hormonal symptoms [1][6][14]. Histologic subtypes include dysgerminomas, yolk sac tumors, and immature teratomas [1][11]. Platinum-based chemotherapy with fertility-sparing surgery achieves cure rates >85%, preserving reproductive function in most cases [3][5][18].
Burden
Incidence: ~1/200,000 females in Europe; higher in Asian/Pacific Islander populations [1][9][17].
Survival: 94–98% 5-year survival for localized disease; drops to 73% for distant metastases [4][16][19].
Long-term risks: Secondary malignancies (2–3%) and premature ovarian insufficiency (17–22%) post-chemotherapy [5][12][18].
Therapies
Fertility-sparing surgery: Unilateral salpingo-oophorectomy ± staging, preserving uterus/contralateral ovary [2][5][18].
Chemotherapy: BEP regimen (bleomycin, etoposide, cisplatin) for advanced stages; EP for bleomycin-ineligible patients [3][5][18].
Relapsed disease: Salvage therapies include ifosfamide, paclitaxel, or high-dose chemo with autologous rescue [3][8][18].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
307 drug discovery papers about Malignant germ cell tumor of ovary, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
307 drug discovery papers about Malignant germ cell tumor of ovary, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-04 | Menstrual Recovery and Reproductive Outcomes After Fertility-Sparing Surgery and Adjuvant Chemotherapy for Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study.
To evaluate menstrual recovery, reproductive outcomes, and survival following fertility-sparing surgery and platinum-based chemotherapy in women with malignant ovarian germ cell tumors (MOGCTs). We retrospectively reviewed women aged 15-40 years with MOGCT treated at a university hospital (2001-2012). All underwent fertility-sparing surgery and platinum-based chemotherapy. Menstrual and reproductive outcomes were assessed through structured interviews and compared with age-matched controls. Survival outcomes were analyzed by Kaplan-Meier method. Among 1934 ovarian cancer cases, 209 (10.8%) were MOGCT; 44 patients met inclusion criteria and were matched to 44 controls. Median age was 21 years; dysgerminoma was the most common histology (40.9%), and 70.4% had Stage I disease. All received bleomycin, etoposide, and cisplatin (median 4 cycles). After a median follow-up of 55 months, 97.7% resumed menstruation. Compared with baseline and controls, cycles were shorter (4 vs. 5 days, p = 0.026), lighter (2 vs. 3 pads/day, p = 0.004-0.047), and longer in interval (29.2 vs. 26.4 days, p < 0.001). Of 17 patients attempting conception, 9 achieved 10 pregnancies, with a pregnancy rate of 52.9% and live-birth rate of 90.9%, without congenital anomalies. Only one recurrence occurred, with 10-year progression-free and overall survival of 95.3% and 97.9%, respectively. Fertility-sparing surgery followed by platinum-based chemotherapy was associated with excellent long-term survival, high rates of menstrual recovery, and favorable reproductive outcomes in young women with MOGCT. These findings support current international recommendations for fertility-preserving treatment in selected patients and provide long-term evidence from a Southeast Asian cohort.
2026-08-28 | Successful Management of Ultra-high-risk Mixed Ovarian Germ Cell Tumor Using a Pediatric-inspired Intensive Chemotherapy Regimen: A Case Report.
Non-gestational ovarian choriocarcinoma is an extremely aggressive malignancy with limited standardized treatment protocols. We present a successful multidisciplinary approach for a high-risk mixed malignant ovarian germ cell tumor (MOGCT) containing a predominant choriocarcinomatous component. A 33-year-old woman presented with acute hemoperitoneum. Pathology confirmed a mixed MOGCT (60% dysgerminoma, 40% choriocarcinoma, focal yolk sac tumor), International Federation of Obstetrics and Gynecology stage IVB. Following optimal cytoreductive surgery, a multidisciplinary tumor board, incorporating pediatric oncology paradigms, initiated a dose-dense, modified regimen of cyclophosphamide, bleomycin, etoposide, cisplatin, and methotrexate (Cy-BEP-MTX), administered every 2 weeks. This intensified strategy aimed to suppress rapid tumor repopulation. The patient tolerated seven cycles of this therapy and achieved complete remission, currently maintaining progression-free survival for 3 years. For ultra-high-risk non-gestational ovarian choriocarcinoma, optimal surgery followed by a pediatric-inspired, dose-dense chemotherapy regimen may provide a superior curative chance compared to standard protocols for adults, highlighting the value of interdisciplinary collaboration.
2026-07-31 | Screening of the antiproliferative activity of lycopene isomers in a panel of human cancer cell lines: Lycopene Z-isomers exhibit greater activity than the all-E-isomer
Abstract Lycopene occurs as multiple geometrical isomers, whereas most studies on its cancer-related effects have focused on the all- E -isomer or on preparations with an undefined isomer composition. In this study, the antiproliferative activities of all- E -isomer-rich lycopene preparation ( E -LYC) and Z -isomer-rich lycopene preparation ( Z -LYC) were compared using a panel of 102 human cancer cell lines under identical experimental conditions. Z -LYC showed a broader antiproliferative profile than E -LYC, with IC 50 values within the tested concentration range (3.16–31,600 nM) in 91 and 16 cell lines, respectively. Tissue sensitivity analysis indicated that lymphoid malignancies and leukemia were relatively sensitive to Z -LYC, with additional sensitivity observed in bone, soft tissue, ovarian, and testicular germ cell tumors. Phenotypic similarity analysis further showed broader correlations for Z -LYC than E -LYC with reference anticancer agents, suggesting a more distinct biological response profile at the cellular level. Preliminary molecular docking simulations also suggested that lycopene Z -isomers may interact more favorably than the all- E -isomer with selected cancer-related proteins. These findings indicate that lycopene Z -isomers exhibit broader antiproliferative activity than the all- E -isomer in this in vitro screening platform and warrant further mechanistic and in vivo studies.
2026-06-30 | An Unclassifiable Malignant Ovarian Germ Cell Tumor With Focal Choriocarcinoma-Like Features: A Case Report With Diagnostic Ambiguity and Adjuvant Treatment Considerations.
Malignant ovarian germ cell tumors (MOGCTs) are uncommon neoplasms with substantial histologic diversity. Although most tumors can be assigned to established subtypes, some tumors show overlapping morphologic and immunophenotypic findings that complicate classification and management. We report a 37-year-old nulligravid woman with a right ovarian tumor, massive ascites, and elevated serum human chorionic gonadotropin (hCG). Histopathological examination revealed heterogeneous findings, including focal yolk sac tumor-like morphology and focal choriocarcinoma-like differentiation. Tumor cells were positive for AE1/AE3 and glypican-3, while AFP, SALL4, OCT4, and CD30 were negative; scattered cells were positive for hCG, GATA3, and p57. The tumor was diagnosed as an unclassifiable malignant ovarian germ cell tumor, International Federation of Gynecology and Obstetrics (FIGO) stage IC1. A key management issue was the postoperative intensity of bleomycin, etoposide, and cisplatin (BEP) chemotherapy. Because of incomplete formal staging and persistent histologic ambiguity, four cycles of BEP were selected rather than treatment de-escalation. The patient remains disease-free on follow-up. This case highlights the following two practical lessons: unusual ovarian germ cell tumors may remain unclassifiable despite integrated pathology, and adjuvant treatment decisions in stage I disease may depend not only on stage but also on staging adequacy and biologic uncertainty.
2026-06-11 | Clinical outcomes of a 3-day modified BEP regimen in malignant ovarian germ cell tumors in a single-center real-world study.
Malignant ovarian germ cell tumors (MOGCTs) mainly affect adolescents and young women and are highly curable with bleomycin, etoposide, and cisplatin (BEP). To reduce toxicity associated with the standard 5-day regimen, we evaluated the efficacy, safety, and fertility outcomes of a 3-day modified BEP regimen in patients with MOGCTs. We conducted a retrospective analysis of 81 MOGCT patients with 3-day modified BEP at the Women's Hospital, Zhejiang University School of Medicine from 2004 to 2024. The 3-day modified BEP regimen comprised bleomycin (15 U) and etoposide (100 mg/m2) on days 1-3, and cisplatin (75 mg/m2) on day 1, repeated every 4 weeks for 3-6 cycles. All 81 MOGCT patients included in our study underwent primary surgery before chemotherapy; 86.4% had early-stage disease, and fertility-sparing surgery was performed in 73 cases. After a median follow-up of over 9 years, the 5-year progression-free survival rate was 97.5% (95% CI: 94.2-100), with no treatment-related deaths. Bleomycin-induced pneumonitis occurred in 4.9% and resolved with supportive care. Among 30 patients attempting conception, 90% achieved pregnancy, resulting in 25 term live births. The 3-day modified BEP regimen provides excellent survival with reduced toxicity, offering greater convenience and preserved fertility, supporting its use as a safer and more practical treatment alternative for initial chemotherapy in MOGCTs.
oligonucleotides
2024-02-26 | [In heritance and innovation in the diagnosis and treatment of malignant ovarian germ cell tumors].
卵巢恶性生殖细胞肿瘤（MOGCT）是最先攻克的卵巢恶性肿瘤，虽然其治疗效果令人满意，肿瘤得到治愈、生殖器官得到保留、生育功能得到保护，满足了患者及医者的期望，但近半个世纪来其诊治方案几乎没有大的改变。近年来，新技术、新药物的发展迅速，对这类肿瘤临床治疗如何守正、如何创新，如何把新技术、新方法应用到诊治中去，如何进一步避免化疗药物的伤害等，都值得所有妇科肿瘤医师积极探讨、深入研究，以期开展更多的临床工作，使MOGCT的诊治更上一层楼。.
2022-03-31 | What is new about germ cell ovarian tumors?
Germ cell tumors of the ovary are the second most frequently found ovarian neoplasms following epithelial ovarian cancers. It is a heterogeneous group with an origin in a primitive germ cells. Therefore, germ cell tumors arise typically in the gonads- ovaries, and testicles. Neoplasms that develop from germ cells in other parts of the body are very rare. Among ovarian germ cell tumors, the most common is a mature teratoma. Tumors such as immature teratoma, dysgerminoma, embryonal carcinoma, or yolk sac tumor appear less frequently. Surgical treatment and chemotherapy, especially a protocol BEP (bleomycin, etoposide, cisplatin) play the most crucial role in the treatment of germ cell malignancies. Before the introduction of systemic chemotherapy, treatment of malignant germ cell tumors of the ovary tended to be poor. The prognosis has improved recently and fertility-conserving surgeries are being performed to enable patients to become pregnant. Additionally, it reduces the risk of late side effects. However, more and more emphasis is placed on developing new methods of treatment and on improving current methods. Some studies showed a therapeutic potential of SOX2 silencing for embryonal carcinoma. The aim of our study was to review the literature to analyze the latest and most effective treatments for embryonic ovarian tumors.
2010-12-09 | Establishment of Cisplatin-Resistant Ovarian Yolk Sac Tumor Cells and Investigation of the Mechanism of Cisplatin Resistance Using This Cell Line
Cisplatin is used as a key drug for ovarian yolk sac tumor (YST), but relapse may occur. Details of the molecular mechanism responsible for cisplatin resistance remain unclear.We established cisplatin-resistant ovarian YST cells (NOY1-CR) from parent NOY1. To characterize these cells, we examined cross-resistance to other anticancer drugs. Then, cDNA microarray analysis was performed to quantify gene expression in NOY1 and NOY1-CR cells. The expression of several potential genes related to drug resistance was compared with parent cells by real-time PCR and Western blotting. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm the genetic association with drug resistance.The IC(50) for cisplatin of NOY1-CR was 22.3-fold higher than that for parent cells. NOY1-CR cells showed cross-resistance to some drugs, but not to VP-16 and bleomycin. Microarray analysis identified 315 up-regulated and 412 down-regulated genes in NOY1-CR cells. Knockdown of GSTA1, which was up-regulated in resistant cells, by GSTA1 siRNA restored cisplatin sensitivity in NOY1-CR cells.Our data suggest the molecular mechanisms of cisplatin resistance and show the potential for GSTA1 to become a novel therapeutic target for cisplatin-resistant ovarian YST.
2008-06-13 | Establishment and Characterization of an Ovarian Yolk Sac Tumor Cell Line Reveals Possible Involvement of Nkx2.5 in Tumor Development
Ovarian yolk sac tumor (YST) is rare and highly malignant. Up to the present, there have been no cell lines of human ovarian YST constructed and, therefore, no studies on their cell function. The purpose of this study was to establish a human ovarian YST cell line to be able to identify a target for novel molecular-based therapy.A 28-year-old woman underwent right salpingo-oophorectomy for right ovarian YST. YST cell lines (NOY1 and NOY2) were established from surgical specimens, and NOY1 cells were characterized. We also transfected them with small interfering RNA (siRNA) oligonucleotides specific for human Nkx2.5 and investigated cell proliferation compared to control siRNA-transfected cells.The cell lines were successfully maintained both in culture and in nude mice. Histological examination showed that xenografted tumors were composed of cells in solid and glandular patterns of YST. These cells were positively immunostained for AFP. Nkx2.5 siRNA-transfected NOY1 cell viability decreased by 50% compared to that of control-siRNA-transfected cells.This is the first report of a cell line established from human YST. Analysis of this new cell line suggested that Nkx2.5 can be a new molecular target in the treatment of ovarian YST.
cell therapies
2026-04-03 | Abstract 496: Oncolinkage: Discovery of tumor-selective surface targets for cancer therapy.
Abstract Cancer therapeutics such as CAR T, Radioligand , ADC, and Bispecifics are all reliant on targeting cancer-selective surface proteins. A major limitation to these tethered killing strategies is the lack of targets that are exclusively expressed on tumor cells and not healthy tissues. Most cancer surface targets exhibit “lineage” expression properties, in which expression is shared by both the tumor and the normal tissue lineage from which the tumor developed. In many cases, expression in normal tissue leads to on-target off-tumor toxicity that can severely limit therapeutic benefit. To address this challenge, we developed Oncolinkage, a computational platform to identify novel tumor targets through their association with genomic changes that drive cancer development. Oncolinkage computationally identifies proteins whose expression is driven by an oncogenic event. While genomic lesions (e.g.amplification, epigenetic dysregulation) activate oncogenes in the developing tumor, many bystander genes are also dysregulated by the non-specific nature of these alterations. Oncolinkage screens for computational signals of cancer genomic lesions mathematically connecting the lesion to target upregulation. Because target expression is “linked” to the pro-tumorigenic lesion, Oncolinked targets are under positive selection, resulting in advantageous properties such as low tumor heterogeneity and resistance to loss. We show that the Cancer/Testis antigens of the MAGE family act as oncolinked targets. Normally restricted to male germ cells, MAGE genes are dysregulated in subsets of multiple solid tumors. Oncolinkage algorithms reveal a distinct set of tumor altered loci that correlate with this tumor-specific expression. We postulate that one or more transcription factors or epigenetic regulators in these loci drives tumor-selective dysregulation of these intracellular targets. Oncolinkage was further used to identify expression-disruptive lesions linked to germ cell restricted surface targets. Among more than a dozen identified oncolinked surface proteins, we found RT1, a protein with testis-restricted expression in normal tissue, but expression in 50% of TNBC and 70% of Ovarian Cancers. Tumor expression was linked to copy number gain on Chr10, the genomic locus of RT1. The known oncogene RET is also present on Chr10 providing a hypothesis that an amplification event targeting the RET oncogene also results in the dysregulation of CAR T target RT1 in subsets of breast and ovarian cancer. The oncolinkage platform is a promising computational approach to identify best-in-class targets for CAR T, RLT, and other tethered killing cancer therapies. Citation Format: McKensie A. Collins, Benjamin T. Hallisey, Andrew Astley, Rick Nicoletti, Murray O. Robinson. Oncolinkage: Discovery of tumor-selective surface targets for cancer therapy [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 496.
2026-04-01 | Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation
Abstract: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Recent evidence suggests that chemotherapy alters exosome cargo, thereby amplifying cellular stress responses, oxidative damage, and bystander effects in gonadal tissues. Conversely, exosomes derived from mesenchymal stem cells, induced pluripotent stem cells (iPSCs), and other regenerative sources demonstrate the ability to restore ovarian and testicular function by reducing apoptosis, enhancing angiogenesis, and supporting germ cell survival. This dual role positions exosomes as both contributors to reproductive toxicity and promising therapeutic agents in fertility preservation strategies. However, clinical translation remains hindered by challenges including source heterogeneity, isolation methods, safety concerns, and regulatory barriers. This review highlights the emerging roles of exosomes in chemotherapy-induced reproductive damage, explores their regenerative potential, and outlines future directions for their integration into oncofertility practice. Lay summary: Cancer treatments such as chemotherapy save lives, but they often damage the ovaries and testes. This can lead to infertility in both women and men, which is one of the most difficult problems for cancer survivors. Finding ways to protect or restore fertility is, therefore, an important part of cancer care. Our work looks at very small particles called exosomes. These are natural messengers that carry proteins and genetic material between cells. We explain how chemotherapy changes these exosomes in a way that increases damage to reproductive organs. At the same time, we show that exosomes from stem cells may help repair this damage. In laboratory studies, they have been shown to protect eggs and sperm and reduce cell death of the reproductive organs during chemotherapy. Exosomes can also act as simple blood-based tests to detect damage and monitor recovery. This research is important because it points to new, less invasive ways to protect fertility during and after cancer treatment. If successful, exosome-based therapies could give patients not only a chance of survival but also the hope of having children in the future.
2025-11-26 | Tumor Microenvironments in Malignant Ovarian Germ Cell Tumors: MHC Class I Loss and T-Cell Exhaustion in Dysgerminoma.
Malignant ovarian germ cell tumors are rare neoplasms primarily affecting young women. Although generally responsive to chemotherapy, long-term adverse effects remain a concern. Improved understanding of the tumor microenvironment may reveal alternative therapeutic strategies; however, comprehensive analyses in malignant ovarian germ cell tumors remain limited. We analyzed 56 malignant ovarian germ cell tumor samples: 23 dysgerminomas, 14 yolk sac tumors, and 19 immature teratomas. Immune cell infiltration and immune checkpoint molecule expression were evaluated via immunohistochemistry, while immune-related gene expression was assessed using transcriptomic profiling. In dysgerminoma, T-cell exhaustion was characterized through multiplex immunofluorescence. Major histocompatibility complex class I expression was assessed across all subtypes. Dysgerminomas showed abundant CD4+ and CD8+ T-cell, B-cell, and M1 macrophage infiltration, with the presence of tertiary lymphoid structures, indicating an immunologically active "hot tumor" phenotype. Immune checkpoint molecules were upregulated, and transcriptomic analysis revealed enrichment of immunostimulatory and immunosuppressive pathways. Conversely, yolk sac tumors were dominated by M2 macrophages, while immature teratomas exhibited minimal immune cell infiltration, a "cold tumor" feature. In dysgerminomas with high programmed cell death protein 1 levels, most CD8+ T cells exhibited a nonexhausted phenotype. All tumor subtypes showed loss of major histocompatibility complex class I expression. These findings indicate that malignant ovarian germ cell tumor subtypes harbor distinct tumor microenvironments, with dysgerminoma characterized by abundant but potentially ineffective T-cell responses owing to absent major histocompatibility complex class I-mediated antigen presentation. Therapeutic strategies restoring major histocompatibility complex class I expression may enhance T cell-based immunotherapy efficacy in dysgerminomas.
2025-10-10 | Fertility preservation in rare ovarian malignancies: a decade-spanning systematic review of menstrual and reproductive outcomes.
Fertility preservation is a growing priority in the management of young women with rare ovarian tumors, including malignant ovarian germ cell tumors (MOGCTs), sex cord-stromal tumors (SCSTs), and borderline ovarian tumors (BOTs). These malignancies often affect adolescents and women of reproductive age and are frequently treated with fertility-sparing surgery and platinum-based chemotherapy. Our objective is to systematically evaluate reproductive outcomes, menstrual function recovery, and fertility preservation strategies in female survivors of rare cancers such as MOGCTs, SCSTs, and BOTs. A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed, Scopus, and BioMed Central were searched for studies published between 2005 and 2025. Eligible studies included observational or cohort designs reporting on fertility status, menstrual recovery, and reproductive outcomes following treatment for rare tumors. A total of 24 studies met the inclusion criteria. Data extraction included fertility preservation approaches, rates of natural versus assisted conception, menstrual function outcomes, and the incidence of premature ovarian insufficiency (POI). Fertility-sparing surgery with or without chemotherapy was the most applied fertility preservation strategy. Spontaneous conception was predominant, with pregnancy rates ranging from 50% to over 90%. Menstrual recovery occurred in 71-100% of patients. POI was rare in solid tumor survivors but occurred in up to 87% of leukemia patients. Long-term follow-up showed durable ovarian function and no increase in cancer recurrence. Ovarian tissue cryopreservation (OTC) and oocyte retrieval were effective in selected high-risk cases. Fertility preservation in patients with rare ovarian malignancies is both safe and effective. Early fertility counseling and individualized, risk-adapted strategies should be integrated into standard cancer care, especially for patients at high risk for gonadal failure.
2025-05-10 | Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system.
Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.
antibodies
2026-04-03 | Abstract 5641: BCG037, a first-in-class anti-human ALPP/ALPG therapeutic ADC that inhibits tumor growth in pancreatic cancer and gastric cancer PDX models.
Abstract Placental (ALPP) and germ cell (ALPG) alkaline phosphatases, sharing 98% sequence homology, are tumor-associated antigens with a highly restricted expression profile. While largely absent in normal adult tissues, they are frequently overexpressed across a wide spectrum of malignancies, including pancreatic, gastric, ovarian, and lung cancers. Elevated ALPP/ALPG levels correlate with poor prognosis in gastric and ovarian cancers, making them compelling targets for antibody-based therapies. Here, we report the development of BCG037, a first-in-class, fully human IgG1 antibody-drug conjugate (ADC) targeting ALPP/ALPG. The antibody was generated from RenMab™ humanized mice and conjugated with the potent topoisomerase I (Top1) inhibitor payload, achieving a high drug-to-antibody ratio (DAR) of ∼8. BCG037 exhibits high affinity (nanomolar range) and cross-reactivity to both human and cynomolgus monkey ALPP/ALPG, with no cross-reactivity to other ALP family members (ALPL, ALPI). Notably, the antibody component of BCG037 demonstrates superior binding affinity to tumor cells compared to the analog used in SGN-ALPV. In vivo, BCG037 treatment led to significant and superior tumor growth inhibition in both pancreatic and gastric cancer patient-derived xenograft (PDX) models, outperforming the benchmark ADC, SGN-ALPV-MMAE, and no treatment-related toxicity or weight loss was observed in mice. Collectively, these data validate ALPP/ALPG as promising therapeutic targets and position BCG037 as a highly novel and potent clinical candidate for treating ALPP/ALPG-positive malignancies, including refractory cancers with limited treatment options. Citation Format: Yong Xie, Peiran Li, Ying Zhu, Yanan Guo. BCG037, a first-in-class anti-human ALPP/ALPG therapeutic ADC that inhibits tumor growth in pancreatic cancer and gastric cancer PDX models [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 5641.
2026-04-03 | Abstract 1620: ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors
Abstract Background Placental alkaline phosphatase (ALPP) and related placental-like/germ-cell isoforms (ALPPL2 / ALPG) are cell-surface alkaline phosphatases that are aberrantly expressed in various solid tumors (e.g., ovarian, endometrial, germ cell, gastric, and pancreatic cancers), while being virtually absent from normal adult tissues except the placenta, making them highly promising tumor-selective targets for immunotherapy. T-cell engagers (TCEs) demonstrate robust clinical activity by co-engaging T cells with tumor cells, thereby inducing T cell activation and T cell-dependent cellular cytotoxicity (TDCC) against tumors. Here we developed ATG-112, an ALPP/G × CD3 bispecific TCE using the AnTenGager™ platform, featuring bivalent antigen binding for improved low-antigen tumor recognition and a sterically-masked CD3 binding arm to restrict T-cell activation to the tumor microenvironment. Methods ATG-112 was engineered in a 2+1 IgG-based format, enabling bivalent binding to ALPP/G and monovalent engagement of CD3. We characterized its binding kinetics, TDCC, immunogenicity, and cytokine release profile using ALPP/G-positive cell lines, recombinant proteins, and human PBMCs. Antitumor efficacy was assessed in humanized mice with HPAC and NCI-H1650 xenografts. Results Tissue microarray (TMA) IHC analysis revealed that ALPP/G expression was restricted to placental tissue in healthy organs and not detected in other normal tissues. In human tumors, ALPP/G was frequently expressed in endometrial (58.50%) and ovarian cancers (51.01%), with lower prevalence in bladder (26.14%), gastric (25.00%), and pancreatic cancers (16.67%). ATG-112 showed high binding affinity to both ALPP/G-positive tumor cells and recombinant protein, with EC50 and KD values in the sub-nanomolar range. ATG-112 induced robust TDCC activity against target positive cells with pico-molar range EC50, confirming potent antigen-dependent T-cell redirection. In vitro cytokine-release assays demonstrated minimal cytokine secretion from human PBMCs, suggesting low risk of excessive immune activation. Immunogenicity assessment showed that humanized ATG-112 molecules exhibited low immunogenic potential. In vivo, ATG-112 achieved potent tumor suppression across multiple dose levels, demonstrating strong antitumor activity and dose responsiveness. Safety studies revealed a favorable in vivo safety profile, including low cytokine release and controllable CRS risk at efficacious doses. ATG-112 also exhibited excellent developability. Conclusion ATG-112 is a 2+1 T-cell engager that potently and selectively targets ALPP/G and CD3. It demonstrates potent in vitro and in vivo efficacy with minimal cytokine release. These findings support ATG-112 as a differentiated and promising therapeutic candidate for ALPP/G-positive solid tumors and justify its advancement toward clinical development. Citation Format: Jishun Chen, Yu Bai, Suya Bai, Huiling Liu, Zaoshun Hu, Jay Mei, Peng Chen, Bing Hou. ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors [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 1620.
2025-05-01 | Advances in the Treatment of Recurrent Ovarian Cancer and Rare Malignant Ovarian Germ Cell Tumors
Most patients with epithelial ovarian cancer will experience recurrence. Treatment at the time of recurrence is largely guided by platinum sensitivity, symptom burden, prior toxicities, and patient preferences. For patients with a first platinum-sensitive recurrence, platinum-based doublets remain the preferred treatment approach. However, changes to care in the United States include the withdrawal of FDA approvals for PARP inhibitors in the recurrent setting for patients without BRCA -mutated disease. The treatment landscape has expanded with the approval of 2 antibody–drug conjugates—mirvetuximab soravtansine-gynx and fam-trastuzumab deruxtecan-nxki—which represent an exciting new class of therapeutics in the oncology pipeline. In contrast, for the rare malignant ovarian germ cell tumors, recurrence is uncommon and cure with up-front treatment is likely. Although progress in this subtype has been slower, treatment in this area is advancing.
2025-04-21 | Abstract 2945: PLB-002 is a novel Claudin 6 antibody-drug conjugate for ovarian cancer and testicular germ cell cancer
Abstract Background: Claudin 6 (CLDN6) is a clinically validated target for many solid tumors notably ovarian, endometrial, and testicular cancer. Its expression is restricted to tumor cells and fetal tissues with little or no detectable in normal tissues. As such, CLDN6 represents an attractive therapeutic target for the development of an antibody drug conjugate (ADC). Here, we describe the development and preclinical characterization of a novel ADC called PLB-002, which consists of a highly selective CLDN6 targeting antibody, PLB-002-ab7, conjugated to a FDA-approved microtubule inhibitor, eribulin, via a Primelink Biotherapeutics proprietary enzyme-cleavable linker with an optimized average drug-to-antibody ratio (DAR) of 4.0. PLB-002-ab7 is a novel humanized anti-CLDN6 single-domain antibody (Mw. 78.8 kDa) with highly binding affinity and selectivity to CLDN6 with barely binding to related CLDN family members (CLDN9, CLDN3, and CLDN4) in protein and cell based binding assays. Methods: The in vitro binding affinity of the PLB-002 was determined by flow cytometry on OVCAR3, PA-1, OVCA429, OV90, and NEC-8 cells. Cell internalization effect was evaluated by an in-direct flow cytometry assay on OVCAR3, PA-1, and OV90 cells. In vitro cytotoxicity was measured using Cell-Titer Glo assay on OVCAR3, OV90, and NEC-8 cells. In vivo anti-tumor efficacy was investigated using several cancer cell derived xenograft (CDX) models of OVCAR3, OV90, and NEC-8 cells, as well as patient derived xenograft (PDX) models of ovarian cancer with CLDN6 high, moderate, low and negative expression. A dose-range finding (DRF) safety study of PLB-002 was performed in cynomolgus monkeys. Pharmacokinetics (PK) and pharmacodynamics (PD) data of PLB-002 in CDX mice were determined by LC-MS/MS method. Results: PLB-002 exhibited strong binding, rapid internalization effect, and potent antitumor activity in vitro on OV90 (CLDN6 low expression) and OVCAR3 (CLDN6 high expression) cells with nano-molar range of IC50. When evaluated in OVCAR3 and OV90 CDXs of ovarian cancer, NEC-8 CDX of testicular germ cell tumor, and OV PDXs, PLB-002 showed strong tumor regression in a dose-dependent manner, which is consistent with the PK analyses showing high exposure, slow clearance and long half-life for both total antibody and conjugated drug. In a non-human primate study using cynomolgus monkey, PLB-002 showed favorable safety profile with no clinical symptoms of toxicities up to the highest tested dose. Conclusions: These results show that PLB-002 has remarkable antitumor activity and support the clinical development as a therapeutic ADC for the treatment of ovarian cancer and other CLDN6 expressing solid cancer. Citation Format: Haitao Pan, Qing Zhang, Ganyuan Xiao, Guangchao Zhang, Jiaxin Li, Ling Xin, Kia J. Puan, Ling Xu, Yingdong Lu, Mao Yin. PLB-002 is a novel Claudin 6 antibody-drug conjugate for ovarian cancer and testicular germ cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2945.
2025-02-10 | A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific antibody in subjects with germ cell tumors and other advanced solid tumors.
TPS652 Background: Claudin-6 (CLDN6) is overexpressed in solid tumors including germ cell tumors (GCTs) with minimal expression in healthy tissue. This differential expression profile makes CLDN6 a suitable tumor-associated antigen for a T-cell engaging bispecific antibody (bsAb). XmAb541 is a first-in-class humanized, anti-CLDN6 x anti-CD3 bsAb that directs T-cell cytotoxicity. The XmAb 2+1 format provides avid tumor targeting and selectivity. Importantly, XmAb541 selectively binds CLDN6, with reduced binding to other claudin family proteins (e.g., CLDN9) and non-CLDN6-expressing healthy tissue [1]. This study focuses on subjects with GCT and other CLDN6+ solid tumors who have failed standard therapy and have a high unmet medical need. The primary objective of the trial is to determine an optimal and tolerated dose(s) for further evaluation. Methods: This is a first-in-human, Phase 1, open-label study to evaluate the safety and tolerability of XmAb541 in advanced solid tumors. The study will be conducted in 2 Parts. Part 1, Dose Escalation, will establish a dosing regimen inclusive of a priming dose, step-up dose(s), and the target dose. Part 2 Dose Expansion will further evaluate safety and tolerability and provide an initial evaluation of preliminary antitumor activity for the dose regimen(s) established in Part 1. XmAb541 will be administered intravenously. Key inclusion criteria are age ≥ 18 years (for subjects with GCTs, age ≥15 years). Have histological evidence of locally advanced, recurrent, or metastatic GCT, ovarian, fallopian tube, peritoneal cancer, or adenocarcinoma of the endometrium. Have documented progressive disease on standard-of-care therapies; exhausted therapies with a survival benefit, or the standard therapy has no survival benefit or proven to be ineffective, intolerable, or subject is not a candidate for such available therapy. Subjects must have an Eastern Cooperative Oncology Group performance status of 0-2 and a life expectancy ≥ 3 months with adequate liver, kidney, and bone marrow function. Key exclusion criteria include the following: known active central nervous system metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate, provided they are radiologically stable. Ethics approval: This study was approved by WCG IRB. References: 1. Faber, M. Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells. (AACR 2021, Abstract No. 1860). Clinical trial information: NCT06276491 .
small molecules
2026-09-04 | Menstrual Recovery and Reproductive Outcomes After Fertility-Sparing Surgery and Adjuvant Chemotherapy for Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study.
To evaluate menstrual recovery, reproductive outcomes, and survival following fertility-sparing surgery and platinum-based chemotherapy in women with malignant ovarian germ cell tumors (MOGCTs). We retrospectively reviewed women aged 15-40 years with MOGCT treated at a university hospital (2001-2012). All underwent fertility-sparing surgery and platinum-based chemotherapy. Menstrual and reproductive outcomes were assessed through structured interviews and compared with age-matched controls. Survival outcomes were analyzed by Kaplan-Meier method. Among 1934 ovarian cancer cases, 209 (10.8%) were MOGCT; 44 patients met inclusion criteria and were matched to 44 controls. Median age was 21 years; dysgerminoma was the most common histology (40.9%), and 70.4% had Stage I disease. All received bleomycin, etoposide, and cisplatin (median 4 cycles). After a median follow-up of 55 months, 97.7% resumed menstruation. Compared with baseline and controls, cycles were shorter (4 vs. 5 days, p = 0.026), lighter (2 vs. 3 pads/day, p = 0.004-0.047), and longer in interval (29.2 vs. 26.4 days, p < 0.001). Of 17 patients attempting conception, 9 achieved 10 pregnancies, with a pregnancy rate of 52.9% and live-birth rate of 90.9%, without congenital anomalies. Only one recurrence occurred, with 10-year progression-free and overall survival of 95.3% and 97.9%, respectively. Fertility-sparing surgery followed by platinum-based chemotherapy was associated with excellent long-term survival, high rates of menstrual recovery, and favorable reproductive outcomes in young women with MOGCT. These findings support current international recommendations for fertility-preserving treatment in selected patients and provide long-term evidence from a Southeast Asian cohort.
2026-08-28 | Successful Management of Ultra-high-risk Mixed Ovarian Germ Cell Tumor Using a Pediatric-inspired Intensive Chemotherapy Regimen: A Case Report.
Non-gestational ovarian choriocarcinoma is an extremely aggressive malignancy with limited standardized treatment protocols. We present a successful multidisciplinary approach for a high-risk mixed malignant ovarian germ cell tumor (MOGCT) containing a predominant choriocarcinomatous component. A 33-year-old woman presented with acute hemoperitoneum. Pathology confirmed a mixed MOGCT (60% dysgerminoma, 40% choriocarcinoma, focal yolk sac tumor), International Federation of Obstetrics and Gynecology stage IVB. Following optimal cytoreductive surgery, a multidisciplinary tumor board, incorporating pediatric oncology paradigms, initiated a dose-dense, modified regimen of cyclophosphamide, bleomycin, etoposide, cisplatin, and methotrexate (Cy-BEP-MTX), administered every 2 weeks. This intensified strategy aimed to suppress rapid tumor repopulation. The patient tolerated seven cycles of this therapy and achieved complete remission, currently maintaining progression-free survival for 3 years. For ultra-high-risk non-gestational ovarian choriocarcinoma, optimal surgery followed by a pediatric-inspired, dose-dense chemotherapy regimen may provide a superior curative chance compared to standard protocols for adults, highlighting the value of interdisciplinary collaboration.
2026-07-31 | Screening of the antiproliferative activity of lycopene isomers in a panel of human cancer cell lines: Lycopene Z-isomers exhibit greater activity than the all-E-isomer
Abstract Lycopene occurs as multiple geometrical isomers, whereas most studies on its cancer-related effects have focused on the all- E -isomer or on preparations with an undefined isomer composition. In this study, the antiproliferative activities of all- E -isomer-rich lycopene preparation ( E -LYC) and Z -isomer-rich lycopene preparation ( Z -LYC) were compared using a panel of 102 human cancer cell lines under identical experimental conditions. Z -LYC showed a broader antiproliferative profile than E -LYC, with IC 50 values within the tested concentration range (3.16–31,600 nM) in 91 and 16 cell lines, respectively. Tissue sensitivity analysis indicated that lymphoid malignancies and leukemia were relatively sensitive to Z -LYC, with additional sensitivity observed in bone, soft tissue, ovarian, and testicular germ cell tumors. Phenotypic similarity analysis further showed broader correlations for Z -LYC than E -LYC with reference anticancer agents, suggesting a more distinct biological response profile at the cellular level. Preliminary molecular docking simulations also suggested that lycopene Z -isomers may interact more favorably than the all- E -isomer with selected cancer-related proteins. These findings indicate that lycopene Z -isomers exhibit broader antiproliferative activity than the all- E -isomer in this in vitro screening platform and warrant further mechanistic and in vivo studies.
2026-06-30 | An Unclassifiable Malignant Ovarian Germ Cell Tumor With Focal Choriocarcinoma-Like Features: A Case Report With Diagnostic Ambiguity and Adjuvant Treatment Considerations.
Malignant ovarian germ cell tumors (MOGCTs) are uncommon neoplasms with substantial histologic diversity. Although most tumors can be assigned to established subtypes, some tumors show overlapping morphologic and immunophenotypic findings that complicate classification and management. We report a 37-year-old nulligravid woman with a right ovarian tumor, massive ascites, and elevated serum human chorionic gonadotropin (hCG). Histopathological examination revealed heterogeneous findings, including focal yolk sac tumor-like morphology and focal choriocarcinoma-like differentiation. Tumor cells were positive for AE1/AE3 and glypican-3, while AFP, SALL4, OCT4, and CD30 were negative; scattered cells were positive for hCG, GATA3, and p57. The tumor was diagnosed as an unclassifiable malignant ovarian germ cell tumor, International Federation of Gynecology and Obstetrics (FIGO) stage IC1. A key management issue was the postoperative intensity of bleomycin, etoposide, and cisplatin (BEP) chemotherapy. Because of incomplete formal staging and persistent histologic ambiguity, four cycles of BEP were selected rather than treatment de-escalation. The patient remains disease-free on follow-up. This case highlights the following two practical lessons: unusual ovarian germ cell tumors may remain unclassifiable despite integrated pathology, and adjuvant treatment decisions in stage I disease may depend not only on stage but also on staging adequacy and biologic uncertainty.
2026-06-11 | Clinical outcomes of a 3-day modified BEP regimen in malignant ovarian germ cell tumors in a single-center real-world study.
Malignant ovarian germ cell tumors (MOGCTs) mainly affect adolescents and young women and are highly curable with bleomycin, etoposide, and cisplatin (BEP). To reduce toxicity associated with the standard 5-day regimen, we evaluated the efficacy, safety, and fertility outcomes of a 3-day modified BEP regimen in patients with MOGCTs. We conducted a retrospective analysis of 81 MOGCT patients with 3-day modified BEP at the Women's Hospital, Zhejiang University School of Medicine from 2004 to 2024. The 3-day modified BEP regimen comprised bleomycin (15 U) and etoposide (100 mg/m2) on days 1-3, and cisplatin (75 mg/m2) on day 1, repeated every 4 weeks for 3-6 cycles. All 81 MOGCT patients included in our study underwent primary surgery before chemotherapy; 86.4% had early-stage disease, and fertility-sparing surgery was performed in 73 cases. After a median follow-up of over 9 years, the 5-year progression-free survival rate was 97.5% (95% CI: 94.2-100), with no treatment-related deaths. Bleomycin-induced pneumonitis occurred in 4.9% and resolved with supportive care. Among 30 patients attempting conception, 90% achieved pregnancy, resulting in 25 term live births. The 3-day modified BEP regimen provides excellent survival with reduced toxicity, offering greater convenience and preserved fertility, supporting its use as a safer and more practical treatment alternative for initial chemotherapy in MOGCTs.
oligonucleotides
2024-02-26 | [In heritance and innovation in the diagnosis and treatment of malignant ovarian germ cell tumors].
卵巢恶性生殖细胞肿瘤（MOGCT）是最先攻克的卵巢恶性肿瘤，虽然其治疗效果令人满意，肿瘤得到治愈、生殖器官得到保留、生育功能得到保护，满足了患者及医者的期望，但近半个世纪来其诊治方案几乎没有大的改变。近年来，新技术、新药物的发展迅速，对这类肿瘤临床治疗如何守正、如何创新，如何把新技术、新方法应用到诊治中去，如何进一步避免化疗药物的伤害等，都值得所有妇科肿瘤医师积极探讨、深入研究，以期开展更多的临床工作，使MOGCT的诊治更上一层楼。.
2022-03-31 | What is new about germ cell ovarian tumors?
Germ cell tumors of the ovary are the second most frequently found ovarian neoplasms following epithelial ovarian cancers. It is a heterogeneous group with an origin in a primitive germ cells. Therefore, germ cell tumors arise typically in the gonads- ovaries, and testicles. Neoplasms that develop from germ cells in other parts of the body are very rare. Among ovarian germ cell tumors, the most common is a mature teratoma. Tumors such as immature teratoma, dysgerminoma, embryonal carcinoma, or yolk sac tumor appear less frequently. Surgical treatment and chemotherapy, especially a protocol BEP (bleomycin, etoposide, cisplatin) play the most crucial role in the treatment of germ cell malignancies. Before the introduction of systemic chemotherapy, treatment of malignant germ cell tumors of the ovary tended to be poor. The prognosis has improved recently and fertility-conserving surgeries are being performed to enable patients to become pregnant. Additionally, it reduces the risk of late side effects. However, more and more emphasis is placed on developing new methods of treatment and on improving current methods. Some studies showed a therapeutic potential of SOX2 silencing for embryonal carcinoma. The aim of our study was to review the literature to analyze the latest and most effective treatments for embryonic ovarian tumors.
2010-12-09 | Establishment of Cisplatin-Resistant Ovarian Yolk Sac Tumor Cells and Investigation of the Mechanism of Cisplatin Resistance Using This Cell Line
Cisplatin is used as a key drug for ovarian yolk sac tumor (YST), but relapse may occur. Details of the molecular mechanism responsible for cisplatin resistance remain unclear.We established cisplatin-resistant ovarian YST cells (NOY1-CR) from parent NOY1. To characterize these cells, we examined cross-resistance to other anticancer drugs. Then, cDNA microarray analysis was performed to quantify gene expression in NOY1 and NOY1-CR cells. The expression of several potential genes related to drug resistance was compared with parent cells by real-time PCR and Western blotting. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm the genetic association with drug resistance.The IC(50) for cisplatin of NOY1-CR was 22.3-fold higher than that for parent cells. NOY1-CR cells showed cross-resistance to some drugs, but not to VP-16 and bleomycin. Microarray analysis identified 315 up-regulated and 412 down-regulated genes in NOY1-CR cells. Knockdown of GSTA1, which was up-regulated in resistant cells, by GSTA1 siRNA restored cisplatin sensitivity in NOY1-CR cells.Our data suggest the molecular mechanisms of cisplatin resistance and show the potential for GSTA1 to become a novel therapeutic target for cisplatin-resistant ovarian YST.
2008-06-13 | Establishment and Characterization of an Ovarian Yolk Sac Tumor Cell Line Reveals Possible Involvement of Nkx2.5 in Tumor Development
Ovarian yolk sac tumor (YST) is rare and highly malignant. Up to the present, there have been no cell lines of human ovarian YST constructed and, therefore, no studies on their cell function. The purpose of this study was to establish a human ovarian YST cell line to be able to identify a target for novel molecular-based therapy.A 28-year-old woman underwent right salpingo-oophorectomy for right ovarian YST. YST cell lines (NOY1 and NOY2) were established from surgical specimens, and NOY1 cells were characterized. We also transfected them with small interfering RNA (siRNA) oligonucleotides specific for human Nkx2.5 and investigated cell proliferation compared to control siRNA-transfected cells.The cell lines were successfully maintained both in culture and in nude mice. Histological examination showed that xenografted tumors were composed of cells in solid and glandular patterns of YST. These cells were positively immunostained for AFP. Nkx2.5 siRNA-transfected NOY1 cell viability decreased by 50% compared to that of control-siRNA-transfected cells.This is the first report of a cell line established from human YST. Analysis of this new cell line suggested that Nkx2.5 can be a new molecular target in the treatment of ovarian YST.
cell therapies
2026-04-03 | Abstract 496: Oncolinkage: Discovery of tumor-selective surface targets for cancer therapy.
Abstract Cancer therapeutics such as CAR T, Radioligand , ADC, and Bispecifics are all reliant on targeting cancer-selective surface proteins. A major limitation to these tethered killing strategies is the lack of targets that are exclusively expressed on tumor cells and not healthy tissues. Most cancer surface targets exhibit “lineage” expression properties, in which expression is shared by both the tumor and the normal tissue lineage from which the tumor developed. In many cases, expression in normal tissue leads to on-target off-tumor toxicity that can severely limit therapeutic benefit. To address this challenge, we developed Oncolinkage, a computational platform to identify novel tumor targets through their association with genomic changes that drive cancer development. Oncolinkage computationally identifies proteins whose expression is driven by an oncogenic event. While genomic lesions (e.g.amplification, epigenetic dysregulation) activate oncogenes in the developing tumor, many bystander genes are also dysregulated by the non-specific nature of these alterations. Oncolinkage screens for computational signals of cancer genomic lesions mathematically connecting the lesion to target upregulation. Because target expression is “linked” to the pro-tumorigenic lesion, Oncolinked targets are under positive selection, resulting in advantageous properties such as low tumor heterogeneity and resistance to loss. We show that the Cancer/Testis antigens of the MAGE family act as oncolinked targets. Normally restricted to male germ cells, MAGE genes are dysregulated in subsets of multiple solid tumors. Oncolinkage algorithms reveal a distinct set of tumor altered loci that correlate with this tumor-specific expression. We postulate that one or more transcription factors or epigenetic regulators in these loci drives tumor-selective dysregulation of these intracellular targets. Oncolinkage was further used to identify expression-disruptive lesions linked to germ cell restricted surface targets. Among more than a dozen identified oncolinked surface proteins, we found RT1, a protein with testis-restricted expression in normal tissue, but expression in 50% of TNBC and 70% of Ovarian Cancers. Tumor expression was linked to copy number gain on Chr10, the genomic locus of RT1. The known oncogene RET is also present on Chr10 providing a hypothesis that an amplification event targeting the RET oncogene also results in the dysregulation of CAR T target RT1 in subsets of breast and ovarian cancer. The oncolinkage platform is a promising computational approach to identify best-in-class targets for CAR T, RLT, and other tethered killing cancer therapies. Citation Format: McKensie A. Collins, Benjamin T. Hallisey, Andrew Astley, Rick Nicoletti, Murray O. Robinson. Oncolinkage: Discovery of tumor-selective surface targets for cancer therapy [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 496.
2026-04-01 | Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation
Abstract: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Recent evidence suggests that chemotherapy alters exosome cargo, thereby amplifying cellular stress responses, oxidative damage, and bystander effects in gonadal tissues. Conversely, exosomes derived from mesenchymal stem cells, induced pluripotent stem cells (iPSCs), and other regenerative sources demonstrate the ability to restore ovarian and testicular function by reducing apoptosis, enhancing angiogenesis, and supporting germ cell survival. This dual role positions exosomes as both contributors to reproductive toxicity and promising therapeutic agents in fertility preservation strategies. However, clinical translation remains hindered by challenges including source heterogeneity, isolation methods, safety concerns, and regulatory barriers. This review highlights the emerging roles of exosomes in chemotherapy-induced reproductive damage, explores their regenerative potential, and outlines future directions for their integration into oncofertility practice. Lay summary: Cancer treatments such as chemotherapy save lives, but they often damage the ovaries and testes. This can lead to infertility in both women and men, which is one of the most difficult problems for cancer survivors. Finding ways to protect or restore fertility is, therefore, an important part of cancer care. Our work looks at very small particles called exosomes. These are natural messengers that carry proteins and genetic material between cells. We explain how chemotherapy changes these exosomes in a way that increases damage to reproductive organs. At the same time, we show that exosomes from stem cells may help repair this damage. In laboratory studies, they have been shown to protect eggs and sperm and reduce cell death of the reproductive organs during chemotherapy. Exosomes can also act as simple blood-based tests to detect damage and monitor recovery. This research is important because it points to new, less invasive ways to protect fertility during and after cancer treatment. If successful, exosome-based therapies could give patients not only a chance of survival but also the hope of having children in the future.
2025-11-26 | Tumor Microenvironments in Malignant Ovarian Germ Cell Tumors: MHC Class I Loss and T-Cell Exhaustion in Dysgerminoma.
Malignant ovarian germ cell tumors are rare neoplasms primarily affecting young women. Although generally responsive to chemotherapy, long-term adverse effects remain a concern. Improved understanding of the tumor microenvironment may reveal alternative therapeutic strategies; however, comprehensive analyses in malignant ovarian germ cell tumors remain limited. We analyzed 56 malignant ovarian germ cell tumor samples: 23 dysgerminomas, 14 yolk sac tumors, and 19 immature teratomas. Immune cell infiltration and immune checkpoint molecule expression were evaluated via immunohistochemistry, while immune-related gene expression was assessed using transcriptomic profiling. In dysgerminoma, T-cell exhaustion was characterized through multiplex immunofluorescence. Major histocompatibility complex class I expression was assessed across all subtypes. Dysgerminomas showed abundant CD4+ and CD8+ T-cell, B-cell, and M1 macrophage infiltration, with the presence of tertiary lymphoid structures, indicating an immunologically active "hot tumor" phenotype. Immune checkpoint molecules were upregulated, and transcriptomic analysis revealed enrichment of immunostimulatory and immunosuppressive pathways. Conversely, yolk sac tumors were dominated by M2 macrophages, while immature teratomas exhibited minimal immune cell infiltration, a "cold tumor" feature. In dysgerminomas with high programmed cell death protein 1 levels, most CD8+ T cells exhibited a nonexhausted phenotype. All tumor subtypes showed loss of major histocompatibility complex class I expression. These findings indicate that malignant ovarian germ cell tumor subtypes harbor distinct tumor microenvironments, with dysgerminoma characterized by abundant but potentially ineffective T-cell responses owing to absent major histocompatibility complex class I-mediated antigen presentation. Therapeutic strategies restoring major histocompatibility complex class I expression may enhance T cell-based immunotherapy efficacy in dysgerminomas.
2025-10-10 | Fertility preservation in rare ovarian malignancies: a decade-spanning systematic review of menstrual and reproductive outcomes.
Fertility preservation is a growing priority in the management of young women with rare ovarian tumors, including malignant ovarian germ cell tumors (MOGCTs), sex cord-stromal tumors (SCSTs), and borderline ovarian tumors (BOTs). These malignancies often affect adolescents and women of reproductive age and are frequently treated with fertility-sparing surgery and platinum-based chemotherapy. Our objective is to systematically evaluate reproductive outcomes, menstrual function recovery, and fertility preservation strategies in female survivors of rare cancers such as MOGCTs, SCSTs, and BOTs. A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed, Scopus, and BioMed Central were searched for studies published between 2005 and 2025. Eligible studies included observational or cohort designs reporting on fertility status, menstrual recovery, and reproductive outcomes following treatment for rare tumors. A total of 24 studies met the inclusion criteria. Data extraction included fertility preservation approaches, rates of natural versus assisted conception, menstrual function outcomes, and the incidence of premature ovarian insufficiency (POI). Fertility-sparing surgery with or without chemotherapy was the most applied fertility preservation strategy. Spontaneous conception was predominant, with pregnancy rates ranging from 50% to over 90%. Menstrual recovery occurred in 71-100% of patients. POI was rare in solid tumor survivors but occurred in up to 87% of leukemia patients. Long-term follow-up showed durable ovarian function and no increase in cancer recurrence. Ovarian tissue cryopreservation (OTC) and oocyte retrieval were effective in selected high-risk cases. Fertility preservation in patients with rare ovarian malignancies is both safe and effective. Early fertility counseling and individualized, risk-adapted strategies should be integrated into standard cancer care, especially for patients at high risk for gonadal failure.
2025-05-10 | Human malignant ovarian germ cell tumor cell lines derived from peritoneal cytology retrieving from circulating tumor cell system.
Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients. We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China). Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients. The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.
antibodies
2026-04-03 | Abstract 5641: BCG037, a first-in-class anti-human ALPP/ALPG therapeutic ADC that inhibits tumor growth in pancreatic cancer and gastric cancer PDX models.
Abstract Placental (ALPP) and germ cell (ALPG) alkaline phosphatases, sharing 98% sequence homology, are tumor-associated antigens with a highly restricted expression profile. While largely absent in normal adult tissues, they are frequently overexpressed across a wide spectrum of malignancies, including pancreatic, gastric, ovarian, and lung cancers. Elevated ALPP/ALPG levels correlate with poor prognosis in gastric and ovarian cancers, making them compelling targets for antibody-based therapies. Here, we report the development of BCG037, a first-in-class, fully human IgG1 antibody-drug conjugate (ADC) targeting ALPP/ALPG. The antibody was generated from RenMab™ humanized mice and conjugated with the potent topoisomerase I (Top1) inhibitor payload, achieving a high drug-to-antibody ratio (DAR) of ∼8. BCG037 exhibits high affinity (nanomolar range) and cross-reactivity to both human and cynomolgus monkey ALPP/ALPG, with no cross-reactivity to other ALP family members (ALPL, ALPI). Notably, the antibody component of BCG037 demonstrates superior binding affinity to tumor cells compared to the analog used in SGN-ALPV. In vivo, BCG037 treatment led to significant and superior tumor growth inhibition in both pancreatic and gastric cancer patient-derived xenograft (PDX) models, outperforming the benchmark ADC, SGN-ALPV-MMAE, and no treatment-related toxicity or weight loss was observed in mice. Collectively, these data validate ALPP/ALPG as promising therapeutic targets and position BCG037 as a highly novel and potent clinical candidate for treating ALPP/ALPG-positive malignancies, including refractory cancers with limited treatment options. Citation Format: Yong Xie, Peiran Li, Ying Zhu, Yanan Guo. BCG037, a first-in-class anti-human ALPP/ALPG therapeutic ADC that inhibits tumor growth in pancreatic cancer and gastric cancer PDX models [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 5641.
2026-04-03 | Abstract 1620: ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors
Abstract Background Placental alkaline phosphatase (ALPP) and related placental-like/germ-cell isoforms (ALPPL2 / ALPG) are cell-surface alkaline phosphatases that are aberrantly expressed in various solid tumors (e.g., ovarian, endometrial, germ cell, gastric, and pancreatic cancers), while being virtually absent from normal adult tissues except the placenta, making them highly promising tumor-selective targets for immunotherapy. T-cell engagers (TCEs) demonstrate robust clinical activity by co-engaging T cells with tumor cells, thereby inducing T cell activation and T cell-dependent cellular cytotoxicity (TDCC) against tumors. Here we developed ATG-112, an ALPP/G × CD3 bispecific TCE using the AnTenGager™ platform, featuring bivalent antigen binding for improved low-antigen tumor recognition and a sterically-masked CD3 binding arm to restrict T-cell activation to the tumor microenvironment. Methods ATG-112 was engineered in a 2+1 IgG-based format, enabling bivalent binding to ALPP/G and monovalent engagement of CD3. We characterized its binding kinetics, TDCC, immunogenicity, and cytokine release profile using ALPP/G-positive cell lines, recombinant proteins, and human PBMCs. Antitumor efficacy was assessed in humanized mice with HPAC and NCI-H1650 xenografts. Results Tissue microarray (TMA) IHC analysis revealed that ALPP/G expression was restricted to placental tissue in healthy organs and not detected in other normal tissues. In human tumors, ALPP/G was frequently expressed in endometrial (58.50%) and ovarian cancers (51.01%), with lower prevalence in bladder (26.14%), gastric (25.00%), and pancreatic cancers (16.67%). ATG-112 showed high binding affinity to both ALPP/G-positive tumor cells and recombinant protein, with EC50 and KD values in the sub-nanomolar range. ATG-112 induced robust TDCC activity against target positive cells with pico-molar range EC50, confirming potent antigen-dependent T-cell redirection. In vitro cytokine-release assays demonstrated minimal cytokine secretion from human PBMCs, suggesting low risk of excessive immune activation. Immunogenicity assessment showed that humanized ATG-112 molecules exhibited low immunogenic potential. In vivo, ATG-112 achieved potent tumor suppression across multiple dose levels, demonstrating strong antitumor activity and dose responsiveness. Safety studies revealed a favorable in vivo safety profile, including low cytokine release and controllable CRS risk at efficacious doses. ATG-112 also exhibited excellent developability. Conclusion ATG-112 is a 2+1 T-cell engager that potently and selectively targets ALPP/G and CD3. It demonstrates potent in vitro and in vivo efficacy with minimal cytokine release. These findings support ATG-112 as a differentiated and promising therapeutic candidate for ALPP/G-positive solid tumors and justify its advancement toward clinical development. Citation Format: Jishun Chen, Yu Bai, Suya Bai, Huiling Liu, Zaoshun Hu, Jay Mei, Peng Chen, Bing Hou. ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors [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 1620.
2025-05-01 | Advances in the Treatment of Recurrent Ovarian Cancer and Rare Malignant Ovarian Germ Cell Tumors
Most patients with epithelial ovarian cancer will experience recurrence. Treatment at the time of recurrence is largely guided by platinum sensitivity, symptom burden, prior toxicities, and patient preferences. For patients with a first platinum-sensitive recurrence, platinum-based doublets remain the preferred treatment approach. However, changes to care in the United States include the withdrawal of FDA approvals for PARP inhibitors in the recurrent setting for patients without BRCA -mutated disease. The treatment landscape has expanded with the approval of 2 antibody–drug conjugates—mirvetuximab soravtansine-gynx and fam-trastuzumab deruxtecan-nxki—which represent an exciting new class of therapeutics in the oncology pipeline. In contrast, for the rare malignant ovarian germ cell tumors, recurrence is uncommon and cure with up-front treatment is likely. Although progress in this subtype has been slower, treatment in this area is advancing.
2025-04-21 | Abstract 2945: PLB-002 is a novel Claudin 6 antibody-drug conjugate for ovarian cancer and testicular germ cell cancer
Abstract Background: Claudin 6 (CLDN6) is a clinically validated target for many solid tumors notably ovarian, endometrial, and testicular cancer. Its expression is restricted to tumor cells and fetal tissues with little or no detectable in normal tissues. As such, CLDN6 represents an attractive therapeutic target for the development of an antibody drug conjugate (ADC). Here, we describe the development and preclinical characterization of a novel ADC called PLB-002, which consists of a highly selective CLDN6 targeting antibody, PLB-002-ab7, conjugated to a FDA-approved microtubule inhibitor, eribulin, via a Primelink Biotherapeutics proprietary enzyme-cleavable linker with an optimized average drug-to-antibody ratio (DAR) of 4.0. PLB-002-ab7 is a novel humanized anti-CLDN6 single-domain antibody (Mw. 78.8 kDa) with highly binding affinity and selectivity to CLDN6 with barely binding to related CLDN family members (CLDN9, CLDN3, and CLDN4) in protein and cell based binding assays. Methods: The in vitro binding affinity of the PLB-002 was determined by flow cytometry on OVCAR3, PA-1, OVCA429, OV90, and NEC-8 cells. Cell internalization effect was evaluated by an in-direct flow cytometry assay on OVCAR3, PA-1, and OV90 cells. In vitro cytotoxicity was measured using Cell-Titer Glo assay on OVCAR3, OV90, and NEC-8 cells. In vivo anti-tumor efficacy was investigated using several cancer cell derived xenograft (CDX) models of OVCAR3, OV90, and NEC-8 cells, as well as patient derived xenograft (PDX) models of ovarian cancer with CLDN6 high, moderate, low and negative expression. A dose-range finding (DRF) safety study of PLB-002 was performed in cynomolgus monkeys. Pharmacokinetics (PK) and pharmacodynamics (PD) data of PLB-002 in CDX mice were determined by LC-MS/MS method. Results: PLB-002 exhibited strong binding, rapid internalization effect, and potent antitumor activity in vitro on OV90 (CLDN6 low expression) and OVCAR3 (CLDN6 high expression) cells with nano-molar range of IC50. When evaluated in OVCAR3 and OV90 CDXs of ovarian cancer, NEC-8 CDX of testicular germ cell tumor, and OV PDXs, PLB-002 showed strong tumor regression in a dose-dependent manner, which is consistent with the PK analyses showing high exposure, slow clearance and long half-life for both total antibody and conjugated drug. In a non-human primate study using cynomolgus monkey, PLB-002 showed favorable safety profile with no clinical symptoms of toxicities up to the highest tested dose. Conclusions: These results show that PLB-002 has remarkable antitumor activity and support the clinical development as a therapeutic ADC for the treatment of ovarian cancer and other CLDN6 expressing solid cancer. Citation Format: Haitao Pan, Qing Zhang, Ganyuan Xiao, Guangchao Zhang, Jiaxin Li, Ling Xin, Kia J. Puan, Ling Xu, Yingdong Lu, Mao Yin. PLB-002 is a novel Claudin 6 antibody-drug conjugate for ovarian cancer and testicular germ cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2945.
2025-02-10 | A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific antibody in subjects with germ cell tumors and other advanced solid tumors.
TPS652 Background: Claudin-6 (CLDN6) is overexpressed in solid tumors including germ cell tumors (GCTs) with minimal expression in healthy tissue. This differential expression profile makes CLDN6 a suitable tumor-associated antigen for a T-cell engaging bispecific antibody (bsAb). XmAb541 is a first-in-class humanized, anti-CLDN6 x anti-CD3 bsAb that directs T-cell cytotoxicity. The XmAb 2+1 format provides avid tumor targeting and selectivity. Importantly, XmAb541 selectively binds CLDN6, with reduced binding to other claudin family proteins (e.g., CLDN9) and non-CLDN6-expressing healthy tissue [1]. This study focuses on subjects with GCT and other CLDN6+ solid tumors who have failed standard therapy and have a high unmet medical need. The primary objective of the trial is to determine an optimal and tolerated dose(s) for further evaluation. Methods: This is a first-in-human, Phase 1, open-label study to evaluate the safety and tolerability of XmAb541 in advanced solid tumors. The study will be conducted in 2 Parts. Part 1, Dose Escalation, will establish a dosing regimen inclusive of a priming dose, step-up dose(s), and the target dose. Part 2 Dose Expansion will further evaluate safety and tolerability and provide an initial evaluation of preliminary antitumor activity for the dose regimen(s) established in Part 1. XmAb541 will be administered intravenously. Key inclusion criteria are age ≥ 18 years (for subjects with GCTs, age ≥15 years). Have histological evidence of locally advanced, recurrent, or metastatic GCT, ovarian, fallopian tube, peritoneal cancer, or adenocarcinoma of the endometrium. Have documented progressive disease on standard-of-care therapies; exhausted therapies with a survival benefit, or the standard therapy has no survival benefit or proven to be ineffective, intolerable, or subject is not a candidate for such available therapy. Subjects must have an Eastern Cooperative Oncology Group performance status of 0-2 and a life expectancy ≥ 3 months with adequate liver, kidney, and bone marrow function. Key exclusion criteria include the following: known active central nervous system metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate, provided they are radiologically stable. Ethics approval: This study was approved by WCG IRB. References: 1. Faber, M. Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells. (AACR 2021, Abstract No. 1860). Clinical trial information: NCT06276491 .
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Drug Discovery Landscape
1 orphan drug designation for Malignant germ cell tumor of ovary.
1 orphan drug designation for Malignant germ cell tumor of ovary.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
squalamine lactate | small molecules | FDA | Genaera Corporation |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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