Elucidating mechanisms of a non-replicating virotherapy to induce the abscopal anti-tumor effects

Virotherapy are expected to elicit systemic anti-tumor effects through the dendric cells-recognition of antigens released from cancer cells killed by virus. Here, we show that a combination therapy of HVJ-E/apolipoproteins with agonist antibodies against T cell co-stimulatory molecules into local tumor lesion significantly represses tumor growth in the target lesion as well as the non-target lesion in mice bearing tumors on both flanks in T cell-dependent manner using multiple cancer cell lines. Transcriptome and T cell repertoire (TCR) analysis of T cells in the target and non-target legions, draining lymph nodes, spleen reveal that the combination therapy of HVJ-E with OX40 agonist antibody in the target lesion activates CD4 and CD8 T cells in the target, non-target lesions, and spleen and promotes migration of CD4 and CD8 T cells from the target to the non-target lesion. Our findings help to understand how systemic anti-tumor effects are induced in tumor and to develop a new therapeutic strategy to elicit systemic anti-tumor effects.