Harnessing SARS-CoV-2-specific CD8+ T cells to kill target tumor cells for cancer immunotherapy

Abstract

List of abbreviations CTL cytotoxic CD8+ T cell HLA human leukocyte antigen MHC-I major histocompatibility complex class I PBMC peripheral blood mononuclear cell pMHCI peptide–MHC-I complex SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 TEDbody CD8+ T cell epitope-delivering antibody Dear Editor, During the coronavirus disease 2019 (COVID-19) pandemic era, many individuals were naturally infected with or vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the presence of cytotoxic CD8+ T cells (CTLs) specific to SARS-CoV-2 antigens, including the spike protein [ 1, 2]. [...]tumor cells were recognized as SARS-CoV-2-infected cells and killed by the spike-specific CTLs (Figure 1A). (J-M) In vivo antitumor efficacy of the TEDbody compared to that of the control antibodies and the mechanism underlying these effects were evaluated in conjunction with the adoptive transfer of ex vivo-expanded spike-specific CTLs in immunodeficient NSG mice carrying pre-established SW480 and SNU-216 cell-derived subcutaneous tumor xenografts (100-120 mm3). [...]their ability to induce target tumor cell lysis, mediated by A*24/S1208- and A*02/S269-CTLs, was limited (Figure 1F-G, Supplementary Figure S3B-C). [...]we optimized the N/C-flanking sequences surrounding the mature CTL epitope using in silico proteasomal cleavage prediction tools [ 8, 9] (Supplementary Figure S4).