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

Frontiers in Immunology

David eKranz¹  Jennifer D. Stone¹ 

[1] University of Illinois, Urbana-Champaign;

关键词: Adoptive T Cell Therapy;    TCR Affinity;    T Cell Sensitivity;    T Cell Cross-Reactivity;    Tumor-Associated Epitopes;   

DOI  :  10.3389/fimmu.2013.00244

来源: DOAJ

【 摘 要 】

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 alpha-beta 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 Fv fragment (scFv) 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 alpha-beta 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.

【 授权许可】

Unknown