TCR-T Cell Recognition of an NY-ESO-1 Epitope Presented by HLA-A2 Supertype: Implications for Cancer Immunotherapy.

Abstract

Background: T-cell receptor (TCR)-engineered T-cell therapy (TCR-T) has become a promising anticancer therapy. Recognition of tumor cells by TCR-T cells requires matched human leukocyte antigen (HLA) alleles and tumor antigens, which seriously limits their population coverage. One strategy to expand the population coverage of a specific TCR-T cell therapy is to enable TCR-T cells to recognize target peptides presented by more HLA alleles.

Methods: In this study, HLA alleles were selected based on the Chinese population frequency and HLA supertype classification. Then, COS-7 and two tumor cell lines (586 mel and 5637) were transduced with selected HLA alleles for functional evaluation of TCR-T cells. HLA-A2 alleles capable of both exogenously and endogenously presenting the NY-ESO-1-derived epitope and thereby being recognized by TCR-T cells were tested.

Results: We demonstrated that a given TCR-T cell product can recognize the NY-ESO-1 peptide exogenously and endogenously presented not only by HLA-A*02:01 but also by HLA-A*02:03, HLA-A*02:06, and HLA-A*02:10, almost doubling the population coverage in the Chinese population from 12.01% to 21.05%.

Conclusions: Our study suggests that cancer patients expressing members of the HLA-A2 supertype may benefit from the TCR-T cell product, and other TCR-T cell products could similarly expand their population coverage even within the non-Chinese population through an analogous approach.