Identification of HPV-E7 specific TCRs for tumor immunotherapy

Abstract

The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E7_89–97/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E7_89–97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.