Oncolytic virotherapy with JX-594 (Pexa-Vec) modulates tumor immune microenvironment to potentiate the efficacy of immune checkpoint blockade
Chan Kim1*, Won Suk Lee1, Hong Jae Chon1 1Laboratory of Tumor Vasculature and Microenvironment, Medical Oncology, CHA University, Seongnam, Republic of Korea *Corresponding Author
Cancer immunotherapy targeting immune checkpoints are now emerging as a promising therapeutic strategy in various tumors. However, the treatment of T-cell non-inflamed tumor which lacks intratumoral T cell infiltrates stand as a clinical hurdle. To overcome the non-inflamed tumor microenvironment, we employed JX-594 (Pexa-Vec), a potent oncolytic vaccinia virus. Localized intratumoral oncolytic virotherapy with JX-594 remodels tumor microenvironment, leading to increased intratumoral T cell infiltration, decreased tumor angiogenesis, and augmented anti-cancer immune response. The anti-tumor immune stimulation caused by localized virotherapy is systemic and tumor-specific, thereby showing potent anti-tumor efficacy in distant, non-treated tumors even if the virus themselves do not spread systemically. Combination of oncolytic vaccinia virus and immune checkpoint inhibitors (ICI) targeting PD-1 or CTLA-4 led to the regression of poorly immunogenic tumors which were resistant to ICI monotherapy. Moreover, optimal sequence and route of administration was critical for the synergistic effects of this combination. Collectively, our findings demonstrate that localized oncolytic virotherapy with JX594 effectively sensitizes non-inflamed tumors to systemic ICI treatment to produce maximal anti-cancer immune response.
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