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Targeting tumor cells toward the antigenic specificity of bystander T cells in tumor microenvironment potentiates cancer immunotherapy

ABSTRACT: Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in tumor microenvironment (TME), leading to the inefficacious immunotherapies in most cancer patients. In contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in TME. To leverage TBYS cells in TME to eradicate tumor cells, we developed an oncolytic virus-based immunotherapy that delivers TBYS cell epitopes (OV-BYTE) into tumor cells, which efficiently redirects the antigen specificity of tumor cells to preexisting TBYS cells and effectively retards tumor growth in multiple preclinical models. Remarkably, the OV-BYTE strategy curtailed tumor progression by targeting SARS-CoV-2-specific T cell memory induced by natural infection or vaccination, providing important insights into the improvement of cancer immunotherapies in a great population with a history of SARS-CoV-2 infection or COVID-19 vaccination.

ORGANISM(S): Mus musculus

PROVIDER: GSE222002 | GEO | 2023/02/02

REPOSITORIES: GEO

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