Combination therapy with oncolytic virus and adoptively transferred T cells or mRNA vaccine amplifies antitumor effects [scRNA-Seq]
Adoptive T-cell therapy or oncolytic virotherapy has made significant progress, but the efficacy was limited by the lack of infiltration into solid tumors when used alone. Here, an oncolytic virus (rVSV-LCMVG) was designed and combined with adoptively transferred T cells. By turning cold tumors hot, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy, whether rVSV-LCMVG was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and sensitized refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD1, and restoring effector-T cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells, and exhibited comparable amplified anti-tumor effects. This study proposed a rational combination therapy of oncolytic virus with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism. Overall design: Comparative gene expression analysis and enrichment analysis of flowcytometry sorted B16-OVA-tumor infiltrating OT1-T cell and P14-T cell RNA-seq data under normal condition and rVSV-LCMVG treatment condition.