RARE DISEASE
Epstein-Barr virus-associated malignant lymphoproliferative disorder
Epstein-Barr virus-associated malignant lymphoproliferative disorder
Epstein-Barr virus-associated malignant lymphoproliferative disorder
Synonyms: EBV-associated lymphoproliferative disorder
Synonyms: EBV-associated lymphoproliferative disorder
Synonyms: EBV-associated lymphoproliferative disorder
Drug discovery
1
drug
With orphan designation
Overview
Epstein-Barr virus (EBV)-associated malignant lymphoproliferative disorders encompass aggressive B-cell or T-cell proliferations driven by latent EBV infection, often arising in immunocompromised individuals. These include post-transplant lymphoproliferative disorder (PTLD), Burkitt lymphoma, Hodgkin lymphoma, and rare NK/T-cell malignancies. Pathogenesis involves disrupted EBV-specific T-cell surveillance, leading to uncontrolled proliferation of infected lymphocytes. Diagnosis relies on histopathology, EBV-encoded RNA (EBER) in situ hybridization, and viral load monitoring [1][3][6][12].
Burden
Therapies
First-line: Rituximab (anti-CD20) ± immunosuppression reduction; EBV-specific cytotoxic T-cell therapy for refractory cases [3][12][18].
Advanced/refractory: Chemotherapy (e.g., CHOP, EPOCH) or CD30-targeted therapy (brentuximab vedotin) [8][11][18].
Prophylaxis: Preemptive rituximab or CTL infusions in high-risk transplant recipients [3][12].
Categories: rare neoplastic diseases
Research Papers
1,131 drug discovery papers about Epstein-Barr virus-associated malignant lymphoproliferative disorder, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,131 drug discovery papers about Epstein-Barr virus-associated malignant lymphoproliferative disorder, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-09-08 | Case Report: Diagnostic pitfall and biomarker-guided therapy in CD20-negative Epstein-Barr virus-positive diffuse large B-cell lymphoma.
De novo CD20-negative Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS), is a rare subtype of DLBCL. CD20 loss complicates both diagnosis and treatment by limiting anti-CD20 antibody use and broadening differential diagnosis. We report a case where comprehensive immunophenotypic and molecular analyses enabled accurate diagnosis. A biomarker-driven strategy combining CD30-targeted therapy and PD-1 blockade achieved a complete metabolic response. This case underscores the importance of biology-based individualized treatment in EBV-associated lymphomas and the need for prospective studies of CD20-independent strategies in high-risk patients.
2026-09-03 | Ectopic Epstein-Barr virus infection in T cells identifies reduced therapeutic responsiveness and immune dysfunction after allogeneic haematopoietic stem cell transplantation.
Epstein-Barr virus (EBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is typically monitored by plasma viral load, but this fails to capture cellular reservoirs. Lineage-specific testing, although usually performed in high-risk patients, may identify biologically distinct disease states. We aimed to evaluate the clinical and biological significance of lineage-specific EBV quantification especially ectopic EBV infection in T cells in allo-HSCT recipients with EBV reactivation. We analysed 144 allo-HSCT recipients with EBV reactivation who underwent lineage-specific EBV quantification, assessed whether T-cell tropic EBV burden identifies a phenotype with reduced responsiveness to rituximab therapy, an increased risk of posttransplant lymphoproliferative disorder (PTLD), and specific features of underlying immune dysfunction. Among the tested high-risk patients with high EBV loads and clinical symptoms, 66.6% exhibited T-cell tropic EBV infection. Compared with non-T-cell tropic infection, T-cell tropism was associated with higher rituximab courses and lower complete response rates (67% vs. 81%, p 0.029), suggesting insufficient efficacy of CD20-directed therapy. Patients with T-cell tropic infection had a significantly higher 1-year cumulative incidence of PTLD compared with the non-T-cell tropic group (77% vs. 41.6%; p <0.001). Single-cell RNA sequencing and mass cytometry analyses revealed an exhausted T-cell phenotype with diminished stemness in T-cell tropic EBV-infected patients. These findings suggest that T-cell EBV quantification distinguishes a therapeutically challenging subtype of EBV reactivation characterized by immune dysfunction and reduced responsiveness to rituximab-based therapy. Incorporating assessment of cellular viral reservoirs into posttransplant EBV monitoring strategies may facilitate early risk stratification and support timely therapeutic escalation beyond rituximab alone.
2026-07-30 | Impact of EBV status and histology on patient outcomes with nivolumab-AVD vs BV-AVD in advanced classic Hodgkin lymphoma (S1826).
Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positive status as well as nonnodular sclerosis (non-NS) histologic subtypes has demonstrated poorer outcomes compared with EBV- and NS tumors. We report a prespecified subset analysis of patients enrolled in the phase 3 SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with N-AVD (nivolumab-AVD) or BV-AVD (brentuximab vedotin-AVD). In the phase 3 SWOG S1826 trial, patients with stage III to IV cHL were randomized to N-AVD or BV-AVD treatment. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in patients who were EBV+ (91% vs 70%; hazard ratio [HR], 0.30; P = .01) and EBV- (90% vs 84%; HR, 0.64; P = .09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS histologic subtypes. N-AVD prolonged 3-year PFS in patients with non-NS histologic subtype (86% vs 63%; HR, 0.33; P = .006) and NS histologic subtype (93% vs 86%; HR, 0.53; P = .01). Non-NS histologic subtype was independently associated with inferior outcomes (HR, 2.54; P< .0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV+ status or non-NS histologic subtype cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = .03 for EBV and HR, 3.08; P< .0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV+ status and non-NS histologic subtype in advanced-stage cHL. These results support N-AVD as a frontline standard of care, particularly in high-risk biologic subgroups. This trial was registered at www.clinicaltrials.gov as NCT03907488.
2026-06-12 | A Comprehensive Literature Review and Case Report of Severe Lymphoproliferative Disease Secondary to CD137 Deficiency.
Inborn errors of immunity, including primary immunodeficiency disorders (PIDs), comprise a heterogeneous group of genetic conditions characterized by immune system dysfunction. One such rare PID is CD137 deficiency, which results from TNFRSF9 mutations. CD137, also known as 4-1BB, plays a pivotal role in immune system regulation and co-stimulation. This literature review explores CD137 deficiency and its implications, emphasizing its association with EBV-associated lymphoproliferative disease and potential therapeutic targets. We present the case of a 21-year-old female patient with CD137 deficiency who experienced recurrent infections, autoimmunity, and lymphoma. Genetic analysis revealed that the patient had a homozygous TNFRSF9 variant. The patient subsequently developed severe Epstein-Barr virus (EBV)-associated lymphoproliferative disease, which is one of the clinical manifestations associated with CD137 deficiency. Additionally, this review discusses similar cases in the literature and details the clinical manifestations and immune abnormalities associated with CD137 deficiency. Understanding the genetic complexity of CD137 deficiency and the immune system dysregulation it causes provides insights into potential therapeutic interventions for affected individuals. This review highlights the role of CD137 as a crucial regulator of immune homeostasis and a potential target for immunotherapy in autoimmune diseases and malignancies.
2026-05-27 | Epstein-Barr Virus-Positive Primary CNS Lymphoma in a Patient Receiving Mycophenolate Mofetil: Diagnostic and Therapeutic Considerations.
Epstein-Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non-germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes.
small molecules
2026-09-23 | DNA methylation dysregulation in EBV-associated lymphoproliferative disorders: molecular mechanisms and therapeutic advances
Epstein-Barr virus–associated lymphoproliferative disorders (EBV-LPDs) are a heterogeneous group of diseases in which aberrant DNA methylation interacts with EBV infection, host genetic mutations, metabolic reprogramming, and immune dysregulation. The purpose of this review is to systematically synthesize current evidence on DNA methylation dysregulation across diverse EBV-LPDs and explore its therapeutic implications, providing a comprehensive overview of the epigenetic mechanisms underlying these disorders. A key feature of EBV-LPDs is the bidirectional interplay between EBV infection and DNA methylation networks: EBV actively remodels both viral and host epigenomes to facilitate latency maintenance and immune evasion, thereby promoting disease progression. Therapeutically, hypomethylating agents have demonstrated clinical activity in selected lymphoma cohorts and can directly remodel the EBV epigenome in vivo. However, most combination trials have not prospectively stratified patients by EBV status. The “epigenetic priming” strategy—using transient epigenetic reprogramming before sequential chemotherapy, immunotherapy, or cellular therapy—is supported by growing preclinical and clinical evidence, although its EBV-specific therapeutic benefit remains to be established. Aberrant DNA methylation contributes to the pathobiology of several EBV-LPDs and represents a potentially actionable therapeutic vulnerability in selected subtypes. However, the absence of standardized epigenetic biomarkers and prospective stratification by EBV status remain major translational barriers. Future studies should prioritize biomarker-guided epigenetic strategies, prospective EBV-status assessment, and preclinical validation of emerging approaches such as CRISPR/dCas9 epigenome editing.
2026-08-20 | Post-transplant Epstein-Barr virus-associated lymphoproliferative disorder after cardiac transplantation: a scoping review.
Post-transplant lymphoproliferative disorder (PTLD) is a serious complication following cardiac transplantation, frequently driven by Epstein-Barr virus (EBV) in the setting of chronic immunosuppression. Despite its clinical significance, data specific to adult cardiac transplant recipients remain fragmented, with variability in reported incidence, risk factors, and outcomes. A scoping review was conducted using the Arksey and O'Malley framework and Joanna Briggs Institute guidelines. Five databases were searched for studies published between 2000 and 2025 focusing on EBV-associated PTLD in adult heart transplant recipients. Inclusion criteria encompassed observational and experimental studies conducted in the United States and Canada. Data extraction and screening were performed using Covidence, with study characteristics, incidence, risk factors, prevention strategies, and outcomes synthesized qualitatively. Six studies met inclusion criteria. PTLD incidence ranged from 0.83% to 5.1%, with 43% to 98% of cases associated with EBV. Donor-positive/recipient-negative EBV serologic mismatch and intensity of immunosuppression were the most consistent risk factors. Median time to PTLD diagnosis ranged from 3.6 to 4.4 years, though late-onset cases were reported. Preventive strategies included EBV PCR surveillance and modification of immunosuppressive regimens, particularly conversion to sirolimus-based therapy. Treatment approaches primarily involved reduction of immunosuppression, rituximab-based therapy, and chemotherapy, with variable outcomes and persistent high morbidity and mortality. EBV-associated PTLD remains a significant complication after cardiac transplantation. Risk stratification based on EBV serostatus and immunosuppression, along with standardized surveillance and tailored therapeutic strategies, is critical to improving outcomes in this high-risk population.
2026-07-05 | Epstein-Barr virus downregulates breast cancer gene 1 to facilitate GPX4-dependent ferroptosis resistance and tumor growth of B-cell lymphoma.
Ferroptosis has emerged as a crucial mechanism in numerous pathological processes such as malignant development. Epstein-Barr virus (EBV) is associated with many malignancies such as B-cell lymphoma (B-CL). However, the role and mechanism of EBV in regulating ferroptosis to participate B-CL development remains poorly understood. Here, we displayed that the expression of breast cancer gene 1 (BRCA1) was downregulated in EBV-infected B-CL cells and tissues. EBV-encoded nuclear antigen 1 (EBNA1) was responsible for the BRCA1 downregulation. Moreover, the expression of BRCA1 was negatively related to that of glutathione peroxidase 4 (GPX4) in B-CL tissues. EBNA1 inhibited ferroptosis by inducing GPX4 expression via BRCA1 inhibition. Mechanistically, BRCA1 bound to GPX4 and promoted GPX4 degradation via the autophagy pathway, thus increasing the sensitivity of EBV-positive B-CL cells to ferroptosis. Furthermore, BRCA1 depletion suppressed ferroptosis in B-CL cells, and the knockdown of endogenous GPX4 in EBV-infected Daudi cells restored ferroptosis sensitivity and markedly suppressed xenograft tumor growth. The findings unveil a novel mechanism by which EBV inhibits ferroptosis for its contribution to the progression of B-CL, identifying a new pathway of BRCA1-mediated GPX4 destabilization. The results provide a new direction for the viral tumorigenicity and potential treatment targets of EBV-related B-CL.
2026-05-16 | A subset of histamine H4 receptor antagonists prevents B lymphocyte proliferation induced by BCR/TLR9 engagement or EBV infection.
Epstein-Barr virus (EBV) infects over 90% of the global population and establishes lifelong latency in memory B cells. In healthy individuals, this latent infection is typically kept in check by the immune system. However, in immunosuppressed patients, EBV can reactivate, leading to uncontrolled B cell proliferation and development of post-transplant lymphoproliferative disorders (PTLD)-a potentially fatal complication. In this study, we demonstrate that a subset of pharmacological antagonists of the histamine H4 receptor (H4R), a G protein-coupled receptor expressed in immune cells, potently suppresses B cell activation and proliferation triggered by BCR/TLR9 engagement or EBV infection. Notably, the lead compound A943931 inhibited transcriptional programs critical for B cell activation, including downregulation of key metabolic genes, resulting in profound suppression of both glycolysis and oxidative phosphorylation. A943931 also blocked EBV-driven B cell immortalization and impaired energy metabolism in lymphoblastoid cell lines, albeit to a lesser extent than in receptor-stimulated B cells. In vivo, A943931 suppressed tumor growth in Daudi Burkitt lymphoma xenografts and prevented B cell lymphoma development in EBV-infected humanized mice. These findings reveal a novel immunometabolic vulnerability of EBV-infected B cells and position this subset of H4R antagonists as promising therapeutic candidates for EBV-associated lymphoproliferative disorders, including PTLD and potentially EBV-linked autoimmune diseases.
2026-05-14 | NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma.
Non-Hodgkin lymphoma (NHL) is one of the most common cancers worldwide, representing 90% of malignant lymphomas. NHL is a diverse group of malignancies, and a subset of these lymphomas are caused by infection with the human gammaherpesvirus, Epstein-Barr virus (EBV). Many EBV-positive lymphomas are highly aggressive and rapidly develop resistance to treatment, leading to poor patient outcomes. Here, we identify the cellular kinase, NEK2, as a therapeutic target for EBV-positive NHL. We demonstrate NEK2 protein expression is increased in primary lymphocytes following EBV infection, and that the EBV latency proteins EBNA1, LMP1, and EBNA2 each independently drive NEK2 upregulation. We show NEK2 is necessary for the growth and survival of EBV-positive NHL, and that NEK2 inhibition selectively kills lymphoma cells but not normal lymphocytes. Inhibition of NEK2 resulted in EBV-specific inflammatory cell death characterized by reactive oxygen species accumulation and gasdermin D cleavage. Additionally, expression of the EBV oncoprotein, LMP1, and the cellular oncoprotein, c-myc, were decreased following NEK2 inhibition. Furthermore, we demonstrate multidrug resistance-associated protein 1 (MRP1) is the most active drug resistance transporter protein in EBV-positive NHL. NEK2 inhibition reduced the expression and activity of cellular drug resistance transporter proteins, including MRP1, leading to increased lymphoma cell chemosensitivity. Finally, using a humanized mouse model of EBV-driven lymphomagenesis, we demonstrate NEK2 inhibition significantly decreased tumor burden and tumor incidence while prolonging survival. Taken together, our data suggest NEK2 inhibition as a promising therapeutic strategy for EBV-positive NHL.
proteins
2026-01-09 | Epstein-Barr Virus-Associated T/NK-Cell Neoplasms.
Epstein-Barr virus (EBV)-associated T- and natural killer (NK)-cell neoplasms encompass a heterogeneous spectrum, ranging from persistent lymphoproliferative disorders (e.g., severe mosquito bite allergy, systemic chronic active EBV disease) to highly aggressive malignancies (e.g., extranodal NK/T-cell lymphoma [ENKTL], aggressive NK-cell leukemia). Genomic and epigenetic studies have revealed shared host genetic alterations-most notably in JAK-STAT signaling, epigenetic regulators, TP53, and DDX3X-supporting a pathogenic and clinicobiological continuum across these disorders. Defective EBV further reshapes viral gene expression programs and contributes to oncogenesis. l-asparaginase-based chemoradiotherapy has improved outcomes in early-stage ENKTL; however, effective treatments for advanced-stage disease and other EBV-associated T/NK-cell neoplasms remain limited. Emerging molecular subclassifications and large-scale prospective cohorts can help clarify disease heterogeneity and accelerate the development of precision therapeutic strategies.
2025-12-27 | Higher chemical complementarity of EBV epitopes and IGH CDR3s correlates with better outcomes for lymphoma and ovarian cancer.
This study investigated the relationship between Epstein-Barr virus (EBV) epitopes and tumor-resident immunoglobulin heavy chain (IGH) CDR3 amino acid (AA) sequences sourced from cancers with a link to EBV. In the case of ovarian cancer, the results revealed that higher chemical complementarity between certain EBV epitopes and IGH CDR3 AA sequences was linked to better outcomes. Additionally, IGH CDR3 and EBV epitope chemical complementarity was examined for Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). For both BL and DLBCL, higher chemical complementarity to certain EBV epitopes was associated with improved overall survival probabilities. This latter result may be relevant to the occasional misdiagnosis of lymphoma for ovarian epithelial carcinoma. In sum, the results justify a more detailed study of the role of EBV and the anti-EBV immune response in the ovarian cancer and lymphoma settings.
2025-11-03 | Ectopic EBV infection in T cells following allogeneic hematopoietic stem cell transplantation: Clinical outcomes and immunological characterization
Abstract Background: Epstein-Barr virus (EBV) infection is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the potential to progress to life-threatening post-transplant lymphoproliferative disorder (PTLD). While EBV primarily targets B cells, emerging clinical evidence demonstrates its capacity for ectopic infection of T cells, which may lead to severe complications such as EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). In allo-HSCT setting, EBV infection of T cells has also been documented, however its clinical significance remains poorly understood, the relationship between T-cell tropic EBV infection and the development of EBV-PTLD is unclear, and the immunological profiles of affected patients have not been systematically characterized. Aims: This study aimed to: (1) evaluate the impact of EBV infection in T cells on post-allo-HSCT outcomes, and (2) delineate the immunological features associated with this high-risk subset of patients. Methods: A total of 147 allo-HSCT patients with EBV infection were enrolled. Lymphocyte subsets were isolated by flow cytometry, and EBV DNA levels were quantitatively assessed. Patients were stratified into two groups based on the infected cell type: T-cell infection group (n = 105) and non–T-cell infection group (n = 42). Clinical parameters—including peak EBV titer, duration of EBV persistence, PTLD development, and transplant outcomes—were compared. Multivariate Cox regression analysis was used to identify risk factors for T-cell infection. High-dimensional immunophenotyping using a 40-marker CyTOF panel was conducted on peripheral blood samples to evaluate differences in immune reconstitution between the two groups. Results: The median time to EBV reactivation was 52 days post-HSCT. Of the cohort, 92 patients (62.6%) developed PTLD, while 55 (37.4%) exhibited asymptomatic EBV DNAemia. The T-cell infection group showed a significantly higher cumulative incidence of PTLD compared to the non–T-cell infection group (69.5% vs. 45.2%, P = 0.010). However, there were no significant differences between the groups in 1-year overall survival (73.3% vs. 81.0%), non-relapse mortality (21.9% vs. 11.9%), incidence of acute graft-versus-host disease (aGVHD) (27.6% vs. 42.9%), or relapse rate (11.4% vs. 16.7%). Early post-transplant EBV DNAemia was identified as an independent risk factor for T-cell infection (P < 0.05). CyTOF analysis revealed markedly impaired interferon-γ (IFN-γ) production in both CD4⁺ and CD8⁺ T cells, indicating T-cell exhaustion in patients with T-cell EBV infection. Conclusion: EBV infection of T cells is associated with a significantly increased risk of PTLD and is characterized by functional exhaustion of T cells. Early EBV reactivation serves as a predictive marker for this high-risk subset, underscoring the need for refined monitoring strategies and targeted immunotherapeutic interventions.
2024-01-11 | Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex.
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1's transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB and JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 and its role in LMP1 signalling remains elusive. Here we demonstrate that TRAF6 interacts directly with a viral TRAF6 binding motif within CTAR2. Functional and NMR studies supported by molecular modeling provide insight into the architecture of the LMP1-TRAF6 complex, which differs from that of CD40-TRAF6. The direct recruitment of TRAF6 to LMP1 is essential for NF-κB activation by CTAR2 and the survival of LMP1-driven lymphoma. Disruption of the LMP1-TRAF6 complex by inhibitory peptides interferes with the survival of EBV-transformed B cells. In this work, we identify LMP1-TRAF6 as a critical virus-host interface and validate this interaction as a potential therapeutic target in EBV-associated cancer.
2023-07-31 | Interleukin-37 is involved in the immunopathogenesis of infectious mononucleosis.
Multiple immunopathological responses to viruses are observed in infectious mononucleosis (IM), a manifestation of primary infection with Epstein-Barr virus (EBV). Protective effects of the negative immunoregulatory molecule interleukin-37 (IL-37) have been observed in various bacterial and viral infections. However, the function of IL-37 in IM remains unknown. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of IL-37 in the peripheral blood of patients diagnosed with IM, and the variation of lymphocyte subsets. Furthermore, the associations between IL-37 expression and the percentage of lymphocyte subgroups were analyzed. Patients with IM had severe immune dysfunction. The control group had a lower expression of IL-37 than the patients with IM. There were significant associations between IL-37 expression and both the proportion of CD3+T cells and the ratio of CD3+CD4+ to CD3+CD8+T cells. Patients with higher levels of IL-37 expression had lower levels of the liver inflammation indicators, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). IL-37 may affect the immune pathogenesis of patients with IM infected with EBV, and may have immunotherapeutic benefit for EBV-associated illnesses.
cell therapies
2026-07-20 | A case of lymphomatoid granulomatosis with renal involvement.
Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated B-cell lymphoproliferative disorder. While LYG mainly causes pulmonary lesions, it is also known to cause extrapulmonary lesions involving the kidney; however, there are limited reports describing the pathology of extrapulmonary lesions in detail. We report the case of an 82-year-old woman who presented with fever and multiple pulmonary nodules, along with elevated urinary β2-microglobulin and proteinuria. A renal biopsy revealed granuloma-like interstitial infiltrates consisting predominantly of CD3+ and CD4+ T lymphocytes with scattered CD20+ B cells and histiocytes. Similar findings on CT-guided lung biopsy raised the possibility of Grade 1 LYG, although a definitive diagnosis could not be established. Following transient clinical improvement with corticosteroids, pulmonary lesions recurred. Subsequent video-assisted thoracoscopic surgery confirmed the presence of Epstein-Barr virus-encoded small (EBER)-RNA positive cells, establishing a final diagnosis of LYG. Detailed descriptions of the renal pathology of LYG are scarce. This case adds to the limited number of reported cases and highlights the value of renal biopsy in excluding alternative diagnoses, particularly when a definitive diagnosis cannot be made using transbronchial or CT-guided lung biopsy.
2026-07-10 | Challenging cases of Epstein-Barr virus positive lymphomas.
Epstein-Barr virus (EBV)-associated lymphomas can develop in both immuno- competent and immunocompromised patients, such as those with human immunodeficiency virus (HIV) infection, other primary or acquired immunodeficiencies, or post transplantation. The current World Health Organization classification consolidated immunodeficiency/dysregulation-related lymphoproliferative disorders into three major histopathological categories: hyperplasia, lymphoproliferative disorder of varied malignant potential, and lymphoma; and reporting the histopathological category, the presence or absence of causally associated viruses (EBV, KSHV/HHV-8), and the immune deficiency/dysregulation setting is recommended. In hematopathology practice, EBV is best confirmed by EBV-encoded RNA in situ hybridization, while immunohistochemistry is used as a complementary test for the presence of EBV-related proteins. Often, additional analyses such as fluorescence in situ hybridization and polymerase chain reaction for B- and T-cell clonality have to be applied for the final classification. This review, summarizing a lecture given at the 10th Course of the Academy of Immunohistochemistry in Cracow, Poland (June 2026), presents some challenging examples of EBV-related lymphomas. Cases include EBV+ mucocutaneous ulcer with subsequent EBV+ diffuse large B-cell lymphoma, EBV+ diffuse large B-cell lymphoma with plasma cell differentiation, post therapy EBV+ Burkitt lymphoma and cutaneous NK/T-cell lymphoma.
2026-07-07 | Post-transplant lymphoproliferative disorder after solid organ transplantation: a comprehensive review
Post-transplant lymphoproliferative disorder (PTLD) is a serious and heterogeneous neoplastic complication of solid organ transplantation (SOT), arising in the setting of sustained pharmacological immunosuppression. This review is specifically focused on PTLD in the SOT setting; PTLD after hematopoietic stem cell transplantation (HSCT) differs substantially in risk factors, pathogenesis, and management, and is beyond the scope of this work. PTLD incidence ranges from 1% to 20%, depending on the grafted organ, with the highest per-procedure rates in intestinal and multiorgan transplants, and the highest absolute case burden in kidney recipients, given transplant volume. PTLD demonstrates a bimodal temporal distribution: an early, predominantly EBV-driven peak at 12–24 months post-transplant, and a late peak at 5–10 years, with a higher proportion of EBV-negative cases. Contemporary evidence suggests a possible decline in early EBV-positive PTLD with improved surveillance, while late-onset EBV-negative PTLD is stable or increasing. EBV establishes latency type III in PTLD-associated B cells, driving proliferation through viral oncoproteins LMP1 and EBNA2. The latency program correlates with histological category and clinical behavior: latency III predominates in early lesions and polymorphic PTLD with strong EBER expression, whereas EBV-negative monomorphic PTLD displays greater genomic complexity, resembling de novo diffuse large B-cell lymphoma (DLBCL), with frequent TP53 mutations and chromosomal gains. The WHO 2022 and ICC 2022 frameworks define four histopathological categories—non-destructive lesions, polymorphic PTLD, monomorphic PTLD, and classic Hodgkin lymphoma (CHL)-type PTLD—each with distinct morphological, immunophenotypic, EBER, and clonality profiles that directly determine treatment intensity. Management follows a sequential strategy: immunosuppression reduction (ISR) as the mainstay first step, followed by rituximab, then chemoimmunotherapy (R-CHOP) for refractory or high-risk disease, with PET/CT-based response assessment using Lugano criteria at each decision point. Tabelecleucel, an allogeneic EBV-specific cytotoxic T-lymphocyte (CTL) product, represents the first approved cellular therapy for refractory EBV-positive PTLD. Immune checkpoint inhibitors carry unacceptably high organ rejection rates and are not recommended for standard PTLD management. Key unmet needs include standardizing EBV surveillance thresholds for preemptive intervention, biomarker-driven risk stratification (PD-L1, LMP1, tumor EBV viral load), and prospective multicenter data on novel immunotherapy combinations in immunosuppressed transplant recipients.
2026-06-23 | Unmanipulated Haploidentical Stem Cell Transplantation Outcome in a Pediatric Patient With CD27 Deficiency and EBV-Induced Diffuse Large B-Cell Lymphoma With Primary CNS Involvement.
CD27 deficiency is a rare primary immunodeficiency associated with severe Epstein-Barr virus (EBV)-related complications, including lymphoma. We report a pediatric patient with CD27 deficiency who developed EBV-associated diffuse large B-cell lymphoma with primary CNS involvement and early relapse. The patient underwent unmanipulated haploidentical stem cell transplantation using post-transplant cyclophosphamide. Engraftment was successful, graft-versus-host disease was controlled, and full donor chimerism was achieved. After 40 months, the patient remains free of GVHD, PID, and lymphoma relapse, demonstrating successful lymphoma control and correction of the underlying immunodeficiency, thereby highlighting the feasibility of haploidentical HSCT in these patients.
2026-06-17 | Clinical presentation, management, and outcomes of post-transplant lymphoproliferative disorder in renal and pancreas transplantation: a 22-year experience
Background Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation associated with long-term immunosuppression and Epstein–Barr virus (EBV) reactivation. This study analyses the clinical presentation, diagnostic pathways, therapeutic strategies and outcomes of PTLD in renal and pancreatic transplant recipients at the Manchester Centre for Transplantation. Methods A retrospective cohort study was carried out on a cohort of 73 patients diagnosed with PTLD between 2002 and 2025 following renal, simultaneous pancreas-kidney (SPK) or pancreas-only transplantation. Data were collected from electronic medical records and analysed descriptively. Clinical presentations were categorised into organ system involvement. Time from presentation to diagnosis and survival outcomes were assessed. Results The median time from transplant to PTLD diagnosis was 132 months, with 56% of cases diagnosed more than 10 years post-transplant. Monomorphic PTLD, in particular diffuse large B-cell lymphoma (DLBCL), was the most common subtype. EBV-positivity was seen in all early cases and in 57% overall. Abdominal and B symptoms were the most frequent presentations. Bleeding and/or anaemia were significantly associated with diagnostic delay ( p = 0.045), and delays over one month were associated with reduced survival ( p = 0.061). Complete or partial remission was achieved in 75% of patients. The 5-year overall survival rate was 68% while 1-year survival was 83% and death-censored graft survival was 82%. Conclusion In our cohort, PTLD in transplant recipients presents with diverse symptoms and can occur several years post-transplant highlighting the need for long-term vigilance. Streamlined referral pathways and increased awareness could reduce diagnostic delays. Establishing a national PTLD registry would benefit future research.
other
2026-05-30 | The rationale for universal use of a prophylactic Epstein-Barr virus vaccine.
Epstein-Barr virus (EBV) was discovered in 1964 by examining cells from a malignant tumor under an electron microscope and as such became the first recognized human cancer virus. Shortly after that, EBV was shown to have infected at least 90% of adults worldwide with infectious mononucleosis being the common clinical manifestation of primary EBV infection. EBV is implicated in the causality of a plethora of malignancies and autoimmune diseases. Recent research studies have strengthened these associations. EBV associated diseases are an enormous global health problem and for that reason we are advocating for the universal use of a prophylactic EBV vaccine to prevent or reduce the severity of these EBV diseases. However, we are aware that a number of unanswered questions need to be addressed in order to maximize the potential benefit of such a vaccine. Perhaps the most important of these is whether an EBV vaccine given after primary EBV infection would confer any protection from the chronic sequelae attributed to EBV.
2026-03-18 | [EBNA1 Knockdown Modulates Proliferation, Apoptosis, and Metabolism in Burkitt's Lymphoma Cells by Downregulating miR-127-5p].
To preliminarily elucidates the role of EBNA1 in epigenetically regulating miR-127-5p and influencing the proliferation, apoptosis, and metabolism of Burkitt's lymphoma (BL) cells. The expression of EBNA1 was knocked down in EBV-positive Raji BL cells through lentiviral shRNA transduction. Gene expression, promoter methylation, and apoptosis were evaluated by quantitative real-time PCR, pyrosequencing, and flow cytometry, respectively. Cell proliferation was assessed by the CCK-8 assay, while cellular glycolytic activity was analyzed using the Seahorse XF Glycolysis Rate Assay. A comparative metabolomic study between EBV-positive Raji cells and EBV-negative CA46 BL cells was conducted using UHPLC-QE-MS. Compared with CA46 cells, the transcriptional level of miR-127-5p was significantly increased in Raji cells (P<0.05). Silencing EBNA1 significantly inhibited Raji cell proliferation, glycolysis level, and miR-127-5p transcriptional level, while promoting Raji cell apoptosis, and increasing Caspase-3 and LCLAT1 protein expression (all P <0.05). Pyrosequencing confirmed that the downregulation of miR-127-5p transcriptional level was associated with increased promoter methylation in EBNA1-shRNAi-Raji cells. Metabolomic analysis revealed that Raji cells produced more tumor metabolism-related metabolites compared to CA46 cells. EBNA1 upregulates the expression of miR-127-5p through demethylation, promoting the proliferation and glycolytic metabolism of EBV+ BL cells, and inhibiting cells apoptosis.
2026-03-11 | Grade 3 Pulmonary Lymphomatoid Granulomatosis Diagnosed by Robotic-Assisted Bronchoscopy: A Case Report.
Lymphomatoid granulomatosis (LYG) is a rare, Epstein-Barr virus (EBV)-associated lymphoproliferative disorder characterized by angiocentric and angiodestructive infiltrates that most commonly involve the lungs. We report a case of a 38-year-old female with a history of latent tuberculosis who presented with a 3-day history of fever, productive cough, bilateral lower extremity edema, and painless lower extremity skin lesions. Initial imaging revealed bilateral pulmonary nodules, and an extensive infectious workup was unrevealing. To obtain diagnostic tissue from peripheral lesions, she underwent robotic-assisted bronchoscopy with targeted transbronchial biopsy. Histopathologic analysis revealed angiocentric and angiodestructive infiltrates with EBV positivity in CD20-positive B cells, consistent with Grade 3 LYG. She was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy, with initial radiographic response. However, she later developed refractory LYG complicated by hemophagocytic lymphohistiocytosis (HLH) and died of progressive disease. Robotic-assisted bronchoscopy enabled safe, targeted sampling of peripheral pulmonary nodules, avoiding more invasive surgical biopsy.
2026-01-07 | Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.
Viruses induce approximately 12% of human cancers, including lymphomas. In the case of T/NK cell neoplasms, human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL), and Epstein-Barr virus (EBV) is associated with extranodal NK/T-cell lymphoma (ENKTCL) and chronic active Epstein-Barr virus disease (CAEBV). Common mechanisms for lymphoma development have been proposed. Viral genes, such as tax and HTLV-1 bZIP factor (HBZ) of HTLV-1, and latent membrane protein 1 (LMP1) and BamHI A rightward transcript microRNA (miRNA-BART) of EBV, contribute to host immune evasion and modulation of host signaling pathways, resulting in the persistence of viral-infected cells. This viral strategy is closely associated with oncogenesis. Furthermore, the long-term survival of infected cells leads to the accumulation of somatic mutations and aberrant epigenetic alterations. These events eventually lead to ATL, ENKTCL, and the lymphoma-like subset of CAEBV. Interrupting these common oncogenic mechanisms is a promising therapeutic strategy for viral-driven lymphomas with poor prognoses.
2026-01-01 | The mRNA vaccine for EBV-LCL delivered by NK EVs
Background: Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) serve as a critical model for EBV-associated lymphoproliferative disorders. Developing an effective mRNA vaccine against EBV-LCL remains challenging due to the inherent instability of mRNA and the lack of safe, efficient, and targeted delivery vehicles. Natural killer (NK) cell-derived extracellular vesicles (EVs) possess unique advantages, including intrinsic tumor-homing ability, low immunogenicity, and favorable biosafety profiles, making them promising next-generation delivery platforms. Objective: This study aims to engineer NK cell-derived EVs as an mRNA vaccine platform targeting EBV-LCL. Specifically, we will employ the CD63-L7Ae system to achieve active and efficient loading of antigen-encoding mRNA into EVs.
antibodies
2026-09-08 | Case Report: Diagnostic pitfall and biomarker-guided therapy in CD20-negative Epstein-Barr virus-positive diffuse large B-cell lymphoma.
De novo CD20-negative Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS), is a rare subtype of DLBCL. CD20 loss complicates both diagnosis and treatment by limiting anti-CD20 antibody use and broadening differential diagnosis. We report a case where comprehensive immunophenotypic and molecular analyses enabled accurate diagnosis. A biomarker-driven strategy combining CD30-targeted therapy and PD-1 blockade achieved a complete metabolic response. This case underscores the importance of biology-based individualized treatment in EBV-associated lymphomas and the need for prospective studies of CD20-independent strategies in high-risk patients.
2026-09-03 | Ectopic Epstein-Barr virus infection in T cells identifies reduced therapeutic responsiveness and immune dysfunction after allogeneic haematopoietic stem cell transplantation.
Epstein-Barr virus (EBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is typically monitored by plasma viral load, but this fails to capture cellular reservoirs. Lineage-specific testing, although usually performed in high-risk patients, may identify biologically distinct disease states. We aimed to evaluate the clinical and biological significance of lineage-specific EBV quantification especially ectopic EBV infection in T cells in allo-HSCT recipients with EBV reactivation. We analysed 144 allo-HSCT recipients with EBV reactivation who underwent lineage-specific EBV quantification, assessed whether T-cell tropic EBV burden identifies a phenotype with reduced responsiveness to rituximab therapy, an increased risk of posttransplant lymphoproliferative disorder (PTLD), and specific features of underlying immune dysfunction. Among the tested high-risk patients with high EBV loads and clinical symptoms, 66.6% exhibited T-cell tropic EBV infection. Compared with non-T-cell tropic infection, T-cell tropism was associated with higher rituximab courses and lower complete response rates (67% vs. 81%, p 0.029), suggesting insufficient efficacy of CD20-directed therapy. Patients with T-cell tropic infection had a significantly higher 1-year cumulative incidence of PTLD compared with the non-T-cell tropic group (77% vs. 41.6%; p <0.001). Single-cell RNA sequencing and mass cytometry analyses revealed an exhausted T-cell phenotype with diminished stemness in T-cell tropic EBV-infected patients. These findings suggest that T-cell EBV quantification distinguishes a therapeutically challenging subtype of EBV reactivation characterized by immune dysfunction and reduced responsiveness to rituximab-based therapy. Incorporating assessment of cellular viral reservoirs into posttransplant EBV monitoring strategies may facilitate early risk stratification and support timely therapeutic escalation beyond rituximab alone.
2026-07-30 | Impact of EBV status and histology on patient outcomes with nivolumab-AVD vs BV-AVD in advanced classic Hodgkin lymphoma (S1826).
Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positive status as well as nonnodular sclerosis (non-NS) histologic subtypes has demonstrated poorer outcomes compared with EBV- and NS tumors. We report a prespecified subset analysis of patients enrolled in the phase 3 SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with N-AVD (nivolumab-AVD) or BV-AVD (brentuximab vedotin-AVD). In the phase 3 SWOG S1826 trial, patients with stage III to IV cHL were randomized to N-AVD or BV-AVD treatment. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in patients who were EBV+ (91% vs 70%; hazard ratio [HR], 0.30; P = .01) and EBV- (90% vs 84%; HR, 0.64; P = .09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS histologic subtypes. N-AVD prolonged 3-year PFS in patients with non-NS histologic subtype (86% vs 63%; HR, 0.33; P = .006) and NS histologic subtype (93% vs 86%; HR, 0.53; P = .01). Non-NS histologic subtype was independently associated with inferior outcomes (HR, 2.54; P< .0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV+ status or non-NS histologic subtype cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = .03 for EBV and HR, 3.08; P< .0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV+ status and non-NS histologic subtype in advanced-stage cHL. These results support N-AVD as a frontline standard of care, particularly in high-risk biologic subgroups. This trial was registered at www.clinicaltrials.gov as NCT03907488.
2026-06-12 | A Comprehensive Literature Review and Case Report of Severe Lymphoproliferative Disease Secondary to CD137 Deficiency.
Inborn errors of immunity, including primary immunodeficiency disorders (PIDs), comprise a heterogeneous group of genetic conditions characterized by immune system dysfunction. One such rare PID is CD137 deficiency, which results from TNFRSF9 mutations. CD137, also known as 4-1BB, plays a pivotal role in immune system regulation and co-stimulation. This literature review explores CD137 deficiency and its implications, emphasizing its association with EBV-associated lymphoproliferative disease and potential therapeutic targets. We present the case of a 21-year-old female patient with CD137 deficiency who experienced recurrent infections, autoimmunity, and lymphoma. Genetic analysis revealed that the patient had a homozygous TNFRSF9 variant. The patient subsequently developed severe Epstein-Barr virus (EBV)-associated lymphoproliferative disease, which is one of the clinical manifestations associated with CD137 deficiency. Additionally, this review discusses similar cases in the literature and details the clinical manifestations and immune abnormalities associated with CD137 deficiency. Understanding the genetic complexity of CD137 deficiency and the immune system dysregulation it causes provides insights into potential therapeutic interventions for affected individuals. This review highlights the role of CD137 as a crucial regulator of immune homeostasis and a potential target for immunotherapy in autoimmune diseases and malignancies.
2026-05-27 | Epstein-Barr Virus-Positive Primary CNS Lymphoma in a Patient Receiving Mycophenolate Mofetil: Diagnostic and Therapeutic Considerations.
Epstein-Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non-germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes.
small molecules
2026-09-23 | DNA methylation dysregulation in EBV-associated lymphoproliferative disorders: molecular mechanisms and therapeutic advances
Epstein-Barr virus–associated lymphoproliferative disorders (EBV-LPDs) are a heterogeneous group of diseases in which aberrant DNA methylation interacts with EBV infection, host genetic mutations, metabolic reprogramming, and immune dysregulation. The purpose of this review is to systematically synthesize current evidence on DNA methylation dysregulation across diverse EBV-LPDs and explore its therapeutic implications, providing a comprehensive overview of the epigenetic mechanisms underlying these disorders. A key feature of EBV-LPDs is the bidirectional interplay between EBV infection and DNA methylation networks: EBV actively remodels both viral and host epigenomes to facilitate latency maintenance and immune evasion, thereby promoting disease progression. Therapeutically, hypomethylating agents have demonstrated clinical activity in selected lymphoma cohorts and can directly remodel the EBV epigenome in vivo. However, most combination trials have not prospectively stratified patients by EBV status. The “epigenetic priming” strategy—using transient epigenetic reprogramming before sequential chemotherapy, immunotherapy, or cellular therapy—is supported by growing preclinical and clinical evidence, although its EBV-specific therapeutic benefit remains to be established. Aberrant DNA methylation contributes to the pathobiology of several EBV-LPDs and represents a potentially actionable therapeutic vulnerability in selected subtypes. However, the absence of standardized epigenetic biomarkers and prospective stratification by EBV status remain major translational barriers. Future studies should prioritize biomarker-guided epigenetic strategies, prospective EBV-status assessment, and preclinical validation of emerging approaches such as CRISPR/dCas9 epigenome editing.
2026-08-20 | Post-transplant Epstein-Barr virus-associated lymphoproliferative disorder after cardiac transplantation: a scoping review.
Post-transplant lymphoproliferative disorder (PTLD) is a serious complication following cardiac transplantation, frequently driven by Epstein-Barr virus (EBV) in the setting of chronic immunosuppression. Despite its clinical significance, data specific to adult cardiac transplant recipients remain fragmented, with variability in reported incidence, risk factors, and outcomes. A scoping review was conducted using the Arksey and O'Malley framework and Joanna Briggs Institute guidelines. Five databases were searched for studies published between 2000 and 2025 focusing on EBV-associated PTLD in adult heart transplant recipients. Inclusion criteria encompassed observational and experimental studies conducted in the United States and Canada. Data extraction and screening were performed using Covidence, with study characteristics, incidence, risk factors, prevention strategies, and outcomes synthesized qualitatively. Six studies met inclusion criteria. PTLD incidence ranged from 0.83% to 5.1%, with 43% to 98% of cases associated with EBV. Donor-positive/recipient-negative EBV serologic mismatch and intensity of immunosuppression were the most consistent risk factors. Median time to PTLD diagnosis ranged from 3.6 to 4.4 years, though late-onset cases were reported. Preventive strategies included EBV PCR surveillance and modification of immunosuppressive regimens, particularly conversion to sirolimus-based therapy. Treatment approaches primarily involved reduction of immunosuppression, rituximab-based therapy, and chemotherapy, with variable outcomes and persistent high morbidity and mortality. EBV-associated PTLD remains a significant complication after cardiac transplantation. Risk stratification based on EBV serostatus and immunosuppression, along with standardized surveillance and tailored therapeutic strategies, is critical to improving outcomes in this high-risk population.
2026-07-05 | Epstein-Barr virus downregulates breast cancer gene 1 to facilitate GPX4-dependent ferroptosis resistance and tumor growth of B-cell lymphoma.
Ferroptosis has emerged as a crucial mechanism in numerous pathological processes such as malignant development. Epstein-Barr virus (EBV) is associated with many malignancies such as B-cell lymphoma (B-CL). However, the role and mechanism of EBV in regulating ferroptosis to participate B-CL development remains poorly understood. Here, we displayed that the expression of breast cancer gene 1 (BRCA1) was downregulated in EBV-infected B-CL cells and tissues. EBV-encoded nuclear antigen 1 (EBNA1) was responsible for the BRCA1 downregulation. Moreover, the expression of BRCA1 was negatively related to that of glutathione peroxidase 4 (GPX4) in B-CL tissues. EBNA1 inhibited ferroptosis by inducing GPX4 expression via BRCA1 inhibition. Mechanistically, BRCA1 bound to GPX4 and promoted GPX4 degradation via the autophagy pathway, thus increasing the sensitivity of EBV-positive B-CL cells to ferroptosis. Furthermore, BRCA1 depletion suppressed ferroptosis in B-CL cells, and the knockdown of endogenous GPX4 in EBV-infected Daudi cells restored ferroptosis sensitivity and markedly suppressed xenograft tumor growth. The findings unveil a novel mechanism by which EBV inhibits ferroptosis for its contribution to the progression of B-CL, identifying a new pathway of BRCA1-mediated GPX4 destabilization. The results provide a new direction for the viral tumorigenicity and potential treatment targets of EBV-related B-CL.
2026-05-16 | A subset of histamine H4 receptor antagonists prevents B lymphocyte proliferation induced by BCR/TLR9 engagement or EBV infection.
Epstein-Barr virus (EBV) infects over 90% of the global population and establishes lifelong latency in memory B cells. In healthy individuals, this latent infection is typically kept in check by the immune system. However, in immunosuppressed patients, EBV can reactivate, leading to uncontrolled B cell proliferation and development of post-transplant lymphoproliferative disorders (PTLD)-a potentially fatal complication. In this study, we demonstrate that a subset of pharmacological antagonists of the histamine H4 receptor (H4R), a G protein-coupled receptor expressed in immune cells, potently suppresses B cell activation and proliferation triggered by BCR/TLR9 engagement or EBV infection. Notably, the lead compound A943931 inhibited transcriptional programs critical for B cell activation, including downregulation of key metabolic genes, resulting in profound suppression of both glycolysis and oxidative phosphorylation. A943931 also blocked EBV-driven B cell immortalization and impaired energy metabolism in lymphoblastoid cell lines, albeit to a lesser extent than in receptor-stimulated B cells. In vivo, A943931 suppressed tumor growth in Daudi Burkitt lymphoma xenografts and prevented B cell lymphoma development in EBV-infected humanized mice. These findings reveal a novel immunometabolic vulnerability of EBV-infected B cells and position this subset of H4R antagonists as promising therapeutic candidates for EBV-associated lymphoproliferative disorders, including PTLD and potentially EBV-linked autoimmune diseases.
2026-05-14 | NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma.
Non-Hodgkin lymphoma (NHL) is one of the most common cancers worldwide, representing 90% of malignant lymphomas. NHL is a diverse group of malignancies, and a subset of these lymphomas are caused by infection with the human gammaherpesvirus, Epstein-Barr virus (EBV). Many EBV-positive lymphomas are highly aggressive and rapidly develop resistance to treatment, leading to poor patient outcomes. Here, we identify the cellular kinase, NEK2, as a therapeutic target for EBV-positive NHL. We demonstrate NEK2 protein expression is increased in primary lymphocytes following EBV infection, and that the EBV latency proteins EBNA1, LMP1, and EBNA2 each independently drive NEK2 upregulation. We show NEK2 is necessary for the growth and survival of EBV-positive NHL, and that NEK2 inhibition selectively kills lymphoma cells but not normal lymphocytes. Inhibition of NEK2 resulted in EBV-specific inflammatory cell death characterized by reactive oxygen species accumulation and gasdermin D cleavage. Additionally, expression of the EBV oncoprotein, LMP1, and the cellular oncoprotein, c-myc, were decreased following NEK2 inhibition. Furthermore, we demonstrate multidrug resistance-associated protein 1 (MRP1) is the most active drug resistance transporter protein in EBV-positive NHL. NEK2 inhibition reduced the expression and activity of cellular drug resistance transporter proteins, including MRP1, leading to increased lymphoma cell chemosensitivity. Finally, using a humanized mouse model of EBV-driven lymphomagenesis, we demonstrate NEK2 inhibition significantly decreased tumor burden and tumor incidence while prolonging survival. Taken together, our data suggest NEK2 inhibition as a promising therapeutic strategy for EBV-positive NHL.
proteins
2026-01-09 | Epstein-Barr Virus-Associated T/NK-Cell Neoplasms.
Epstein-Barr virus (EBV)-associated T- and natural killer (NK)-cell neoplasms encompass a heterogeneous spectrum, ranging from persistent lymphoproliferative disorders (e.g., severe mosquito bite allergy, systemic chronic active EBV disease) to highly aggressive malignancies (e.g., extranodal NK/T-cell lymphoma [ENKTL], aggressive NK-cell leukemia). Genomic and epigenetic studies have revealed shared host genetic alterations-most notably in JAK-STAT signaling, epigenetic regulators, TP53, and DDX3X-supporting a pathogenic and clinicobiological continuum across these disorders. Defective EBV further reshapes viral gene expression programs and contributes to oncogenesis. l-asparaginase-based chemoradiotherapy has improved outcomes in early-stage ENKTL; however, effective treatments for advanced-stage disease and other EBV-associated T/NK-cell neoplasms remain limited. Emerging molecular subclassifications and large-scale prospective cohorts can help clarify disease heterogeneity and accelerate the development of precision therapeutic strategies.
2025-12-27 | Higher chemical complementarity of EBV epitopes and IGH CDR3s correlates with better outcomes for lymphoma and ovarian cancer.
This study investigated the relationship between Epstein-Barr virus (EBV) epitopes and tumor-resident immunoglobulin heavy chain (IGH) CDR3 amino acid (AA) sequences sourced from cancers with a link to EBV. In the case of ovarian cancer, the results revealed that higher chemical complementarity between certain EBV epitopes and IGH CDR3 AA sequences was linked to better outcomes. Additionally, IGH CDR3 and EBV epitope chemical complementarity was examined for Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). For both BL and DLBCL, higher chemical complementarity to certain EBV epitopes was associated with improved overall survival probabilities. This latter result may be relevant to the occasional misdiagnosis of lymphoma for ovarian epithelial carcinoma. In sum, the results justify a more detailed study of the role of EBV and the anti-EBV immune response in the ovarian cancer and lymphoma settings.
2025-11-03 | Ectopic EBV infection in T cells following allogeneic hematopoietic stem cell transplantation: Clinical outcomes and immunological characterization
Abstract Background: Epstein-Barr virus (EBV) infection is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with the potential to progress to life-threatening post-transplant lymphoproliferative disorder (PTLD). While EBV primarily targets B cells, emerging clinical evidence demonstrates its capacity for ectopic infection of T cells, which may lead to severe complications such as EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). In allo-HSCT setting, EBV infection of T cells has also been documented, however its clinical significance remains poorly understood, the relationship between T-cell tropic EBV infection and the development of EBV-PTLD is unclear, and the immunological profiles of affected patients have not been systematically characterized. Aims: This study aimed to: (1) evaluate the impact of EBV infection in T cells on post-allo-HSCT outcomes, and (2) delineate the immunological features associated with this high-risk subset of patients. Methods: A total of 147 allo-HSCT patients with EBV infection were enrolled. Lymphocyte subsets were isolated by flow cytometry, and EBV DNA levels were quantitatively assessed. Patients were stratified into two groups based on the infected cell type: T-cell infection group (n = 105) and non–T-cell infection group (n = 42). Clinical parameters—including peak EBV titer, duration of EBV persistence, PTLD development, and transplant outcomes—were compared. Multivariate Cox regression analysis was used to identify risk factors for T-cell infection. High-dimensional immunophenotyping using a 40-marker CyTOF panel was conducted on peripheral blood samples to evaluate differences in immune reconstitution between the two groups. Results: The median time to EBV reactivation was 52 days post-HSCT. Of the cohort, 92 patients (62.6%) developed PTLD, while 55 (37.4%) exhibited asymptomatic EBV DNAemia. The T-cell infection group showed a significantly higher cumulative incidence of PTLD compared to the non–T-cell infection group (69.5% vs. 45.2%, P = 0.010). However, there were no significant differences between the groups in 1-year overall survival (73.3% vs. 81.0%), non-relapse mortality (21.9% vs. 11.9%), incidence of acute graft-versus-host disease (aGVHD) (27.6% vs. 42.9%), or relapse rate (11.4% vs. 16.7%). Early post-transplant EBV DNAemia was identified as an independent risk factor for T-cell infection (P < 0.05). CyTOF analysis revealed markedly impaired interferon-γ (IFN-γ) production in both CD4⁺ and CD8⁺ T cells, indicating T-cell exhaustion in patients with T-cell EBV infection. Conclusion: EBV infection of T cells is associated with a significantly increased risk of PTLD and is characterized by functional exhaustion of T cells. Early EBV reactivation serves as a predictive marker for this high-risk subset, underscoring the need for refined monitoring strategies and targeted immunotherapeutic interventions.
2024-01-11 | Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex.
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) drives viral B cell transformation and oncogenesis. LMP1's transforming activity depends on its C-terminal activation region 2 (CTAR2), which induces NF-κB and JNK by engaging TNF receptor-associated factor 6 (TRAF6). The mechanism of TRAF6 recruitment to LMP1 and its role in LMP1 signalling remains elusive. Here we demonstrate that TRAF6 interacts directly with a viral TRAF6 binding motif within CTAR2. Functional and NMR studies supported by molecular modeling provide insight into the architecture of the LMP1-TRAF6 complex, which differs from that of CD40-TRAF6. The direct recruitment of TRAF6 to LMP1 is essential for NF-κB activation by CTAR2 and the survival of LMP1-driven lymphoma. Disruption of the LMP1-TRAF6 complex by inhibitory peptides interferes with the survival of EBV-transformed B cells. In this work, we identify LMP1-TRAF6 as a critical virus-host interface and validate this interaction as a potential therapeutic target in EBV-associated cancer.
2023-07-31 | Interleukin-37 is involved in the immunopathogenesis of infectious mononucleosis.
Multiple immunopathological responses to viruses are observed in infectious mononucleosis (IM), a manifestation of primary infection with Epstein-Barr virus (EBV). Protective effects of the negative immunoregulatory molecule interleukin-37 (IL-37) have been observed in various bacterial and viral infections. However, the function of IL-37 in IM remains unknown. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of IL-37 in the peripheral blood of patients diagnosed with IM, and the variation of lymphocyte subsets. Furthermore, the associations between IL-37 expression and the percentage of lymphocyte subgroups were analyzed. Patients with IM had severe immune dysfunction. The control group had a lower expression of IL-37 than the patients with IM. There were significant associations between IL-37 expression and both the proportion of CD3+T cells and the ratio of CD3+CD4+ to CD3+CD8+T cells. Patients with higher levels of IL-37 expression had lower levels of the liver inflammation indicators, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). IL-37 may affect the immune pathogenesis of patients with IM infected with EBV, and may have immunotherapeutic benefit for EBV-associated illnesses.
cell therapies
2026-07-20 | A case of lymphomatoid granulomatosis with renal involvement.
Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-associated B-cell lymphoproliferative disorder. While LYG mainly causes pulmonary lesions, it is also known to cause extrapulmonary lesions involving the kidney; however, there are limited reports describing the pathology of extrapulmonary lesions in detail. We report the case of an 82-year-old woman who presented with fever and multiple pulmonary nodules, along with elevated urinary β2-microglobulin and proteinuria. A renal biopsy revealed granuloma-like interstitial infiltrates consisting predominantly of CD3+ and CD4+ T lymphocytes with scattered CD20+ B cells and histiocytes. Similar findings on CT-guided lung biopsy raised the possibility of Grade 1 LYG, although a definitive diagnosis could not be established. Following transient clinical improvement with corticosteroids, pulmonary lesions recurred. Subsequent video-assisted thoracoscopic surgery confirmed the presence of Epstein-Barr virus-encoded small (EBER)-RNA positive cells, establishing a final diagnosis of LYG. Detailed descriptions of the renal pathology of LYG are scarce. This case adds to the limited number of reported cases and highlights the value of renal biopsy in excluding alternative diagnoses, particularly when a definitive diagnosis cannot be made using transbronchial or CT-guided lung biopsy.
2026-07-10 | Challenging cases of Epstein-Barr virus positive lymphomas.
Epstein-Barr virus (EBV)-associated lymphomas can develop in both immuno- competent and immunocompromised patients, such as those with human immunodeficiency virus (HIV) infection, other primary or acquired immunodeficiencies, or post transplantation. The current World Health Organization classification consolidated immunodeficiency/dysregulation-related lymphoproliferative disorders into three major histopathological categories: hyperplasia, lymphoproliferative disorder of varied malignant potential, and lymphoma; and reporting the histopathological category, the presence or absence of causally associated viruses (EBV, KSHV/HHV-8), and the immune deficiency/dysregulation setting is recommended. In hematopathology practice, EBV is best confirmed by EBV-encoded RNA in situ hybridization, while immunohistochemistry is used as a complementary test for the presence of EBV-related proteins. Often, additional analyses such as fluorescence in situ hybridization and polymerase chain reaction for B- and T-cell clonality have to be applied for the final classification. This review, summarizing a lecture given at the 10th Course of the Academy of Immunohistochemistry in Cracow, Poland (June 2026), presents some challenging examples of EBV-related lymphomas. Cases include EBV+ mucocutaneous ulcer with subsequent EBV+ diffuse large B-cell lymphoma, EBV+ diffuse large B-cell lymphoma with plasma cell differentiation, post therapy EBV+ Burkitt lymphoma and cutaneous NK/T-cell lymphoma.
2026-07-07 | Post-transplant lymphoproliferative disorder after solid organ transplantation: a comprehensive review
Post-transplant lymphoproliferative disorder (PTLD) is a serious and heterogeneous neoplastic complication of solid organ transplantation (SOT), arising in the setting of sustained pharmacological immunosuppression. This review is specifically focused on PTLD in the SOT setting; PTLD after hematopoietic stem cell transplantation (HSCT) differs substantially in risk factors, pathogenesis, and management, and is beyond the scope of this work. PTLD incidence ranges from 1% to 20%, depending on the grafted organ, with the highest per-procedure rates in intestinal and multiorgan transplants, and the highest absolute case burden in kidney recipients, given transplant volume. PTLD demonstrates a bimodal temporal distribution: an early, predominantly EBV-driven peak at 12–24 months post-transplant, and a late peak at 5–10 years, with a higher proportion of EBV-negative cases. Contemporary evidence suggests a possible decline in early EBV-positive PTLD with improved surveillance, while late-onset EBV-negative PTLD is stable or increasing. EBV establishes latency type III in PTLD-associated B cells, driving proliferation through viral oncoproteins LMP1 and EBNA2. The latency program correlates with histological category and clinical behavior: latency III predominates in early lesions and polymorphic PTLD with strong EBER expression, whereas EBV-negative monomorphic PTLD displays greater genomic complexity, resembling de novo diffuse large B-cell lymphoma (DLBCL), with frequent TP53 mutations and chromosomal gains. The WHO 2022 and ICC 2022 frameworks define four histopathological categories—non-destructive lesions, polymorphic PTLD, monomorphic PTLD, and classic Hodgkin lymphoma (CHL)-type PTLD—each with distinct morphological, immunophenotypic, EBER, and clonality profiles that directly determine treatment intensity. Management follows a sequential strategy: immunosuppression reduction (ISR) as the mainstay first step, followed by rituximab, then chemoimmunotherapy (R-CHOP) for refractory or high-risk disease, with PET/CT-based response assessment using Lugano criteria at each decision point. Tabelecleucel, an allogeneic EBV-specific cytotoxic T-lymphocyte (CTL) product, represents the first approved cellular therapy for refractory EBV-positive PTLD. Immune checkpoint inhibitors carry unacceptably high organ rejection rates and are not recommended for standard PTLD management. Key unmet needs include standardizing EBV surveillance thresholds for preemptive intervention, biomarker-driven risk stratification (PD-L1, LMP1, tumor EBV viral load), and prospective multicenter data on novel immunotherapy combinations in immunosuppressed transplant recipients.
2026-06-23 | Unmanipulated Haploidentical Stem Cell Transplantation Outcome in a Pediatric Patient With CD27 Deficiency and EBV-Induced Diffuse Large B-Cell Lymphoma With Primary CNS Involvement.
CD27 deficiency is a rare primary immunodeficiency associated with severe Epstein-Barr virus (EBV)-related complications, including lymphoma. We report a pediatric patient with CD27 deficiency who developed EBV-associated diffuse large B-cell lymphoma with primary CNS involvement and early relapse. The patient underwent unmanipulated haploidentical stem cell transplantation using post-transplant cyclophosphamide. Engraftment was successful, graft-versus-host disease was controlled, and full donor chimerism was achieved. After 40 months, the patient remains free of GVHD, PID, and lymphoma relapse, demonstrating successful lymphoma control and correction of the underlying immunodeficiency, thereby highlighting the feasibility of haploidentical HSCT in these patients.
2026-06-17 | Clinical presentation, management, and outcomes of post-transplant lymphoproliferative disorder in renal and pancreas transplantation: a 22-year experience
Background Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation associated with long-term immunosuppression and Epstein–Barr virus (EBV) reactivation. This study analyses the clinical presentation, diagnostic pathways, therapeutic strategies and outcomes of PTLD in renal and pancreatic transplant recipients at the Manchester Centre for Transplantation. Methods A retrospective cohort study was carried out on a cohort of 73 patients diagnosed with PTLD between 2002 and 2025 following renal, simultaneous pancreas-kidney (SPK) or pancreas-only transplantation. Data were collected from electronic medical records and analysed descriptively. Clinical presentations were categorised into organ system involvement. Time from presentation to diagnosis and survival outcomes were assessed. Results The median time from transplant to PTLD diagnosis was 132 months, with 56% of cases diagnosed more than 10 years post-transplant. Monomorphic PTLD, in particular diffuse large B-cell lymphoma (DLBCL), was the most common subtype. EBV-positivity was seen in all early cases and in 57% overall. Abdominal and B symptoms were the most frequent presentations. Bleeding and/or anaemia were significantly associated with diagnostic delay ( p = 0.045), and delays over one month were associated with reduced survival ( p = 0.061). Complete or partial remission was achieved in 75% of patients. The 5-year overall survival rate was 68% while 1-year survival was 83% and death-censored graft survival was 82%. Conclusion In our cohort, PTLD in transplant recipients presents with diverse symptoms and can occur several years post-transplant highlighting the need for long-term vigilance. Streamlined referral pathways and increased awareness could reduce diagnostic delays. Establishing a national PTLD registry would benefit future research.
other
2026-05-30 | The rationale for universal use of a prophylactic Epstein-Barr virus vaccine.
Epstein-Barr virus (EBV) was discovered in 1964 by examining cells from a malignant tumor under an electron microscope and as such became the first recognized human cancer virus. Shortly after that, EBV was shown to have infected at least 90% of adults worldwide with infectious mononucleosis being the common clinical manifestation of primary EBV infection. EBV is implicated in the causality of a plethora of malignancies and autoimmune diseases. Recent research studies have strengthened these associations. EBV associated diseases are an enormous global health problem and for that reason we are advocating for the universal use of a prophylactic EBV vaccine to prevent or reduce the severity of these EBV diseases. However, we are aware that a number of unanswered questions need to be addressed in order to maximize the potential benefit of such a vaccine. Perhaps the most important of these is whether an EBV vaccine given after primary EBV infection would confer any protection from the chronic sequelae attributed to EBV.
2026-03-18 | [EBNA1 Knockdown Modulates Proliferation, Apoptosis, and Metabolism in Burkitt's Lymphoma Cells by Downregulating miR-127-5p].
To preliminarily elucidates the role of EBNA1 in epigenetically regulating miR-127-5p and influencing the proliferation, apoptosis, and metabolism of Burkitt's lymphoma (BL) cells. The expression of EBNA1 was knocked down in EBV-positive Raji BL cells through lentiviral shRNA transduction. Gene expression, promoter methylation, and apoptosis were evaluated by quantitative real-time PCR, pyrosequencing, and flow cytometry, respectively. Cell proliferation was assessed by the CCK-8 assay, while cellular glycolytic activity was analyzed using the Seahorse XF Glycolysis Rate Assay. A comparative metabolomic study between EBV-positive Raji cells and EBV-negative CA46 BL cells was conducted using UHPLC-QE-MS. Compared with CA46 cells, the transcriptional level of miR-127-5p was significantly increased in Raji cells (P<0.05). Silencing EBNA1 significantly inhibited Raji cell proliferation, glycolysis level, and miR-127-5p transcriptional level, while promoting Raji cell apoptosis, and increasing Caspase-3 and LCLAT1 protein expression (all P <0.05). Pyrosequencing confirmed that the downregulation of miR-127-5p transcriptional level was associated with increased promoter methylation in EBNA1-shRNAi-Raji cells. Metabolomic analysis revealed that Raji cells produced more tumor metabolism-related metabolites compared to CA46 cells. EBNA1 upregulates the expression of miR-127-5p through demethylation, promoting the proliferation and glycolytic metabolism of EBV+ BL cells, and inhibiting cells apoptosis.
2026-03-11 | Grade 3 Pulmonary Lymphomatoid Granulomatosis Diagnosed by Robotic-Assisted Bronchoscopy: A Case Report.
Lymphomatoid granulomatosis (LYG) is a rare, Epstein-Barr virus (EBV)-associated lymphoproliferative disorder characterized by angiocentric and angiodestructive infiltrates that most commonly involve the lungs. We report a case of a 38-year-old female with a history of latent tuberculosis who presented with a 3-day history of fever, productive cough, bilateral lower extremity edema, and painless lower extremity skin lesions. Initial imaging revealed bilateral pulmonary nodules, and an extensive infectious workup was unrevealing. To obtain diagnostic tissue from peripheral lesions, she underwent robotic-assisted bronchoscopy with targeted transbronchial biopsy. Histopathologic analysis revealed angiocentric and angiodestructive infiltrates with EBV positivity in CD20-positive B cells, consistent with Grade 3 LYG. She was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy, with initial radiographic response. However, she later developed refractory LYG complicated by hemophagocytic lymphohistiocytosis (HLH) and died of progressive disease. Robotic-assisted bronchoscopy enabled safe, targeted sampling of peripheral pulmonary nodules, avoiding more invasive surgical biopsy.
2026-01-07 | Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.
Viruses induce approximately 12% of human cancers, including lymphomas. In the case of T/NK cell neoplasms, human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL), and Epstein-Barr virus (EBV) is associated with extranodal NK/T-cell lymphoma (ENKTCL) and chronic active Epstein-Barr virus disease (CAEBV). Common mechanisms for lymphoma development have been proposed. Viral genes, such as tax and HTLV-1 bZIP factor (HBZ) of HTLV-1, and latent membrane protein 1 (LMP1) and BamHI A rightward transcript microRNA (miRNA-BART) of EBV, contribute to host immune evasion and modulation of host signaling pathways, resulting in the persistence of viral-infected cells. This viral strategy is closely associated with oncogenesis. Furthermore, the long-term survival of infected cells leads to the accumulation of somatic mutations and aberrant epigenetic alterations. These events eventually lead to ATL, ENKTCL, and the lymphoma-like subset of CAEBV. Interrupting these common oncogenic mechanisms is a promising therapeutic strategy for viral-driven lymphomas with poor prognoses.
2026-01-01 | The mRNA vaccine for EBV-LCL delivered by NK EVs
Background: Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) serve as a critical model for EBV-associated lymphoproliferative disorders. Developing an effective mRNA vaccine against EBV-LCL remains challenging due to the inherent instability of mRNA and the lack of safe, efficient, and targeted delivery vehicles. Natural killer (NK) cell-derived extracellular vesicles (EVs) possess unique advantages, including intrinsic tumor-homing ability, low immunogenicity, and favorable biosafety profiles, making them promising next-generation delivery platforms. Objective: This study aims to engineer NK cell-derived EVs as an mRNA vaccine platform targeting EBV-LCL. Specifically, we will employ the CD63-L7Ae system to achieve active and efficient loading of antigen-encoding mRNA into EVs.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Epstein-Barr virus-associated malignant lymphoproliferative disorder.
1 orphan drug designation for Epstein-Barr virus-associated malignant lymphoproliferative disorder.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Allogeneic CD4+ and CD8+ T lymphocytes ex vivo incubated with synthetic peptides of the viral antigens of cytomegalovirus, adenovirus and Epstein-Barr virus | cell therapies | EMA | Miltenyi Biotec GmbH |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.