Rapidly Expanded EBV-Specific T Cells for the Treatment of Refractory EBV Reactivation and EBV-Related...

Latent Epstein-Barr virus (EBV) infection is asymptomatic in most adults but can be associated with lymphoma, particularly in immunocompromised patients. Options are limited for patients with EBV viremia disease refractory to B-cell depleting antibodies or chemotherapy. Cellular therapies targeting EBV have shown promise in treating EBV-associated malignancies and restoring anti-EBV immunity.

This is a phase I/II clinical trial in 9 patients, along with 3 additional single-patient trial cases, evaluating patient-specific manufacturing and administration of virus-specific T cells (VSTs) from various sources for the treatment or prevention of EBV-related lymphoma. The VSTs were produced from autologous and allogeneic peripheral blood mononuclear cells (PBMCs) using synthetic viral peptides stimulation.

Three patients were allogeneic hematopoietic stem cell transplant (HCT) recipients, 4 were solid organ transplant (SOT) recipients, and 2 were nontransplant patients with EBV-associated lymphoma. VSTs were successfully manufactured from healthy donors and demonstrated strong and specific reactivity to EBV. Six patients achieved or maintained complete responses (3 SOT and 3 HCT) while 3 did not respond to therapy (1 SOT recipient and 2 nontransplant patients), resulting in an overall response rate of 67% (86% in transplant patients). One patient died of noninfusion related complications during the study follow-up period. Cell infusions were well tolerated with no treatment-related serious adverse events reported.

These results strengthen previously published results using VSTs from healthy donors and further support the development of EBV-specific T cell therapies to treat refractory EBV reactivation and EBV-associated malignancies, particularly in transplant recipients.