Personalized neoantigen vaccine enhances the therapeutic efficacy of bevacizumab and anti PD-1 antibody in advanced non-small cell lung cancer (PRJCA018707)

Clinically, chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC). But due to the systemic toxicity of chemotherapy, some patients cannot tolerate or even resist. Here, we intend to develop a chemotherapy-free treatment combination, that is, neoantigen vaccine combined with bevacizumab and anti PD-1 antibody, to provide a new treatment strategy option for advanced NSCLC patients. Firstly, 7 immunogenic neoantigen peptides for LLC were identified to prepare LLCvac, which could induce a strong immune response and show good antitumor effect. Furthermore, in orthotopic LLC lung cancer model, when neoantigen vaccine combining with bevacizumab and anti PD-1 antibody, it could exert a stronger anti-tumor effect with significantly decreasing of all tumor volume and without increasing obvious toxicity. Tumor immune microenvironment assessment also showed that the combined therapy could significantly elicit an increase in the proportion of neoantigen-specific T cells in both blood and tumors when compared with control groups and could induce more neoantigen-specific Ki67-positive CD8 T cells infiltrating into tumor tissues to further specific kill tumor cells expressing identified neoantigen. Overall, these results suggested that these combined therapy could induce potent robust antitumor efficacy in NSCLC with good safety and could serve as a feasible chemotherapy-free treatment combination.