LAUSR

Significance Harnessing the heterogeneity of the cancer antigenic landscape to induce antitumor T cells is at the basis of personalized vaccines and adoptive T cell–transfer therapies. However, these highly personalized approaches remain associated with limited efficacy against most solid tumors and manufacturing complexities, whose high costs of development and implementation have limited their impact as public health interventions. Using murine cancer models, we report a tumor antigen–agnostic approach based on intratumoral injection of virus-derived peptide epitopes to mobilize vigorous antiviral T cell responses. This strategy does not require the characterization of tumor-associated antigens, and it can mobilize vigorous, cytotoxic T cell responses in the tumor microenvironment and promote epitope spreading against tumor-associated antigens.