Combination immunotherapy of oncolytic virus nanovesicles and PD-1 blockade effectively enhances therapeutic effects and boosts antitumour immune response

Immunotherapies are changing the landscape of melanoma treatment, but 70% of the melanoma patients have no response to immune checkpoint inhibitors or oncolytic virus therapy. Thus, novel formulations are needed to improve the population benefiting from immunotherapy. Here, we report a combined therapeutic modality based on oncolytic virus nanovesicles composed of CaCl2, oncolytic virus Ad5, lecithin and cholesterol (Lipo-Cap-Ad5) with immune checkpoint blockade (anti-PD-1 antibody). We investigated in vivo antitumour activity, systemic toxicity and mechanism of antitumour immune responses of Lipo-Cap-Ad5 + anti-PD-1 blockade, in a murine B16F10 tumour xenograft model. Through a series of in vivo studies, we found that Lipo-Cap-Ad5 in combination with anti-PD-1 blockade drastically reduced the tumour growth by 76.6%, and prolonged animals' survival with no obvious toxicity observed in heart, liver and kidney. The combination therapy facilitates tumour infiltration of effector CD4(+), CD8(+) T cells and increases secretion of TNF-alpha and IFN-gamma. Therefore, Lipo-Cap-Ad5 in combination with anti-PD-1 blockade can potentiate and activate the immune system synergistically, ultimately creating a pro-inflammatory environment. These results suggest that combination immunotherapy of Lipo-Cap-Ad5 and anti-PD-1 blockade developed in this study has promising applications to enhance therapeutic efficacy with the potential of being translated into clinical practice.