Virus-specific T-cells from third party or transplant donors for treatment of EBV lymphoproliferative diseases arising post hematopoietic cell or solid organ transplantation

Front Immunol. 2024 Jan 11:14:1290059. doi: 10.3389/fimmu.2023.1290059. eCollection 2023.

Abstract

EBV+ lymphomas constitute a significant cause of morbidity and mortality in recipients of allogeneic hematopoietic cell (HCT) and solid organ transplants (SOT). Phase I and II trials have shown that in HCT recipients, adoptive transfer of EBV-specific T-cells from the HCT donor can safely induce durable remissions of EBV+ lymphomas including 70->90% of patients who have failed to respond to treatment with Rituximab. More recently, EBV-specific T-cells generated from allogeneic 3rd party donors have also been shown to induce durable remission of EBV+ lymphomas in Rituximab refractory HCT and SOT recipients. In this review, we compare results of phase I and II trials of 3rd party and donor derived EBV-specific T-cells. We focus on the attributes and limitations of each product in terms of access, safety, responses achieved and durability. The limited data available regarding donor and host factors contributing to T cell persistence is also described. We examine factors contributing to treatment failures and approaches to prevent or salvage relapse. Lastly, we summarize strategies to further improve results for virus-specific immunotherapies for post-transplant EBV lymphomas.

Keywords: EBV-CTLs; Epstein-Barr virus (EBV); T-cells; lymphoma; lymphoproliferative disorder; third party; transplantation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Epstein-Barr Virus Infections* / complications
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Herpesvirus 4, Human
  • Humans
  • Lymphoma* / therapy
  • Lymphoproliferative Disorders* / etiology
  • Lymphoproliferative Disorders* / therapy
  • Neoplasm Recurrence, Local / complications
  • Organ Transplantation* / adverse effects
  • Rituximab / therapeutic use
  • T-Lymphocytes
  • Tissue Donors

Substances

  • Rituximab