Immune checkpoint inhibitor therapies currently benefit only a subset of patients in the clinic because the majority of patients bear “cold” tumors with low pre-infiltration of effector T cells and low expression of checkpoint inhibitors. Therefore, there is a critical need for an effective strategy that can not only recruit effector T cells into tumor microenvironment, but also broaden the repertoire of T cells engaged in the existing checkpoint inhibitor therapies that stimulate antitumor activity. Here, we hypothesized cowpea mosaic virus (CPMV) could induce effector CD4+ and CD8+ T cells infiltration into tumors and induce PD-1 expression on effector T cells, leading to more susceptible targets for anti-PD-1 immunotherapy. We demonstrated that in situ CPMV administration recruited both CD4+ and CD8+ T cells to the tumor site and induced the expression of PD-1 on those T cells using an immunocompetent murine ovarian cancer model, therefore, enhancing the targeting performance of PD-1 blockade and triggering robust local cytotoxic T cell immune responses. The combination of CPMV and anti-PD-1 worked synergistically to delay tumor growth and prevent tumor relapse. This work may lead to new design principles for plant virus nanoparticles as novel immunotherapeutic adjuvants and provide new treatment option for ovarian cancer patients.

Combination of cowpea mosaic virus and PD-1 blockade works synergistically to improve therapeutic efficacy

2019 Fall National Meeting

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