Rapidly Expanded EBV-Specific T Cells for the Treatment of Refractory EBV Reactivation and EBV-Related Lymphoproliferative Disorders - Report - MDSpire
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Rapidly Expanded EBV-Specific T Cells for the Treatment of Refractory EBV Reactivation and EBV-Related Lymphoproliferative Disorders
Accelerated EBV-Specific T Cells for Refractory EBV Reactivation and Lymphoproliferative Disorders
Overview
This phase I/II trial evaluated rapidly expanded EBV-specific virus-specific T cells (VSTs) in 12 patients with refractory EBV reactivation or EBV-associated lymphoma. The therapy showed a 67% overall response rate, with 86% response in transplant recipients, and was well tolerated without serious treatment-related adverse events.
Background
Epstein–Barr virus (EBV) establishes lifelong latency in B cells and can cause lymphoma, especially in immunocompromised patients such as transplant recipients. Post-transplant lymphoproliferative disorder (PTLD) is a serious complication with limited treatment options, particularly when refractory to B-cell depleting antibodies or chemotherapy. Adoptive transfer of EBV-specific T cells has emerged as a promising therapy to restore antiviral immunity and treat EBV-associated malignancies. Rapid manufacturing of these cellular therapies is critical due to the aggressive nature of refractory EBV-related diseases.
Data Highlights
Patient Group
Number of Patients
Complete Response
Non-Response
Overall Response Rate
HCT Recipients
3
3
0
100%
SOT Recipients
4
3
1
75%
Nontransplant Patients
2
0
2
0%
Total
9
6
3
67%
Key Findings
Rapidly expanded EBV-specific VSTs were successfully manufactured from both autologous and allogeneic PBMCs using synthetic viral peptides.
Six out of nine patients in the clinical trial achieved or maintained complete responses, including all three hematopoietic stem cell transplant (HCT) recipients and three solid organ transplant (SOT) recipients.
Three patients did not respond to therapy, including one SOT recipient and two nontransplant patients with EBV-associated lymphoma.
Overall response rate was 67%, increasing to 86% among transplant recipients.
Cell infusions were well tolerated with no treatment-related serious adverse events reported.
One patient died due to non-infusion related complications during follow-up.
Clinical Implications
Rapid expansion of EBV-specific T cells provides a feasible and effective therapeutic option for managing refractory EBV reactivation and EBV-associated lymphoproliferative disorders, especially in transplant recipients. This approach can overcome limitations of conventional therapies and offers a safe treatment alternative with promising response rates. The rapid manufacturing process is critical for timely intervention in aggressive disease settings.
Conclusion
Rapidly expanded EBV-specific VST therapy demonstrates safety and efficacy in treating refractory EBV-related lymphoproliferative disorders, particularly in transplant patients, supporting further development and clinical application of this cellular immunotherapy.
References
Clinical Trials and Therapeutics Major Article -- Accelerated Development of EBV-Specific T Cells for Managing Refractory EBV Reactivation and EBV-Associated Lymphoproliferative Disorders
