T cell optimization for graft-versus-leukemia responses

JCI Insight. 2020 May 7;5(9):e134939. doi: 10.1172/jci.insight.134939.

Abstract

Protection from relapse after allogeneic hematopoietic cell transplantation (HCT) is partly due to donor T cell-mediated graft-versus-leukemia (GVL) immune responses. Relapse remains common in HCT recipients, but strategies to augment GVL could significantly improve outcomes after HCT. Donor T cells with αβ T cell receptors (TCRs) mediate GVL through recognition of minor histocompatibility antigens and alloantigens in HLA-matched and -mismatched HCT, respectively. αβ T cells specific for other leukemia-associated antigens, including nonpolymorphic antigens and neoantigens, may also deliver an antileukemic effect. γδ T cells may contribute to GVL, although their biology and specificity are less well understood. Vaccination or adoptive transfer of donor-derived T cells with natural or transgenic receptors are strategies with potential to selectively enhance αβ and γδ T cell GVL effects.

Publication types

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

MeSH terms

  • Adult
  • Cell Line
  • Child
  • Graft Enhancement, Immunologic
  • Graft vs Leukemia Effect / immunology*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Minor Histocompatibility Antigens / immunology*
  • T-Lymphocytes* / cytology
  • T-Lymphocytes* / immunology

Substances

  • Minor Histocompatibility Antigens