Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies

Jennifer D. Stone, David M. Kranz

Research output: Contribution to journalReview article

Abstract

Over the last several years, there has been considerable progress in the treatment of cancer using gene modified adoptive T cell therapies. Two approaches have been used, one involving the introduction of a conventional αβ T cell receptor (TCR) against a pepMHC cancer antigen, and the second involving introduction of a chimeric antigen receptor (CAR) consisting of a single-chain antibody as an Fvfragment linked to transmembrane and signaling domains. In this review, we focus on one aspect of TCR-mediated adoptive T cell therapies, the impact of the affinity of the aß TCR for the pepMHC cancer antigen on both efficacy and specificity. We discuss the advantages of higher-affinity TCRs in mediating potent activity of CD4 T cells. This is balanced with the potential disadvantage of higher-affinity TCRs in mediating greater self-reactivity against a wider range of structurally similar antigenic peptides, especially in synergy with the CD8 co-receptor. Both TCR affinity and target selection will influence potential safety issues. We suggest pre-clinical strategies that might be used to examine each TCR for possible on-target and off-target side effects due to self-reactivities, and to adjust TCR affinities accordingly.

Original languageEnglish (US)
Article numberArticle 244
JournalFrontiers in immunology
Volume4
Issue numberAUG
DOIs
StatePublished - 2013

Keywords

  • Adoptive T cell therapy
  • T cell cross-reactivity
  • T cell sensitivity
  • TCR affinity
  • Tumor-associated epitopes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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