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

Abstract

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-α and IFN-γ. 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.

Keywords:

• Combination immunotherapy
• oncolytic virus
• nanovesicles
• immune checkpoint inhibitors
• melanoma

Disclosure statement

The authors report no conflicts of interest. The authors are responsible for the content and writing of the paper.

Additional information

Funding

The authors gratefully acknowledge National Natural Science Foundation of China [Grant No. 81402575].