Immune responses elicited by rMV-SLAMblind oncolytic therapy exert a synergistic effect on cancer therapy

Abstract Oncolytic virotherapy has emerged as a promising strategy for cancer therapy. rMV-SLAMblind is a recombinant measles virus that lacks the ability to interact with SLAM and specifically infects and lyses NECTIN4 + cancer cells. We previously reported that rMV-SLAMblind oncolytic virotherapy (rMV-OVT) exerts anti-tumor immunity through the activation of immune cells in virus-treated tumors. It is thought that oncolytic virotherapy promotes anti-tumor effects via two mechanisms: direct tumor cell lysis caused by infection and the induction of immune cell-mediated tumor cell death. However, it is unknown whether the immune cells activated by rMV-OVT exert anti-tumor effects on non-treated tumors and whether rMV-SLAMblind enhances the effects of immune checkpoint blockade. This study demonstrated that rMV-OVT suppressed the growth of non-treated tumors in a bilateral tumor mouse model and enhanced anti-tumor effects in combination therapy with anti-PD1 antibody. Notably, CD4 + T cell depletion led to the trends towards favorable anti-tumor effects of rMV-OVT in some cases, which was accompanied by increasing numbers of activated CD8 + T cells. These results suggest that rMV-OVT demonstrated efficacy via immune cell-mediated tumor cell death, which was improved by combination therapy with immune checkpoint inhibitors. These findings provide valuable insights into improving the efficacy of rMV-OVT for cancer therapy.