Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted

Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456.

Abstract

Infection with adenoviruses is a common and significant complication in pediatric patients after allogeneic hematopoietic stem cell transplantation. Treatment options with traditional antivirals are limited by poor efficacy and significant toxicities. T-cell reconstitution is critical for the management of adenoviral infections, but it generally takes place months after transplantation. Ex vivo-generated virus-specific T cells (VSTs) are an alternative approach for viral control and can be rapidly generated from either a stem cell donor or a healthy third-party donor. In the context of a single-center phase 1/2 clinical trial, we treated 30 patients with a total of 43 infusions of VSTs for adenoviremia and/or adenoviral disease. Seven patients received donor-derived VSTs, 21 patients received third-party VSTs, and 2 received VSTs from both donor sources. Clinical responses were observed in 81% of patients, with a complete response in 58%. Epitope prediction and potential epitope identification for common HLA molecules helped elucidate HLA restriction in a subset of patients receiving third-party products. Intracellular interferon-γ expression in T cells in response to single peptides and response to cell lines stably transfected with a single HLA molecule demonstrated HLA-restricted CD4+ T-cell response, and these results correlated with clinical outcomes. Taken together, these data suggest that VSTs are a highly safe and effective therapy for the management of adenoviral infection in immunocompromised hosts. The trials were registered at www.clinicaltrials.gov as #NCT02048332 and #NCT02532452.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae Infections* / therapy
  • Child
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Interferon-gamma
  • Stem Cell Transplantation / adverse effects
  • T-Lymphocytes

Substances

  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT02048332
  • ClinicalTrials.gov/NCT02532452