Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD‐1 blockade

Abstract

AbstractThe global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti‐neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV‐LAV) against KC. The findings clearly demonstrate that PRV‐LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV‐LAV was confirmed in both a subcutaneous tumor‐bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA‐seq analysis and flow cytometry revealed that PRV‐LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV‐LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV‐LAV with anti‐PD‐1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV‐LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.