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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.