Combination with oxaliplatin improves abscopal effect of oncolytic virotherapy through reorganization of intratumoral macrophages

Oncolytic virotherapy is a unique and promising immunotherapy. In our prior study, a recombinant oncolytic vaccinia virus carrying IL-7 and IL-12 (hIL-7/mIL-12-VV) showed robust antitumor efficacy in both immunogenic CT26.WT and poorly immunogenic Lewis lung carcinoma (LLC) within the treated tumors. However, the efficacy was limited in virus non-treated (distant) LLC tumors. Here we identified oxaliplatin as a powerful combination partner for an oncolytic vaccinia virus to achieve strong efficacy in the virus-injected tumors and the distant tumors. To understand the molecular mechanism of enhanced antitumor efficacy, we evaluated RNA-sequencing signatures in LLC tumors treated with oxaliplatin alone, hIL-7/mIL-12-VV alone and their combination.