Chemotherapy-induced nanovaccines implement immunogenicity equivalence for improving cancer chemoimmunotherapy

Several chemoimmunotherapies have been approved by the FDA for the treatment of various cancers. Chemotherapy has the potential to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of tumor cells, promoting the release of tumor associated antigens (TAAs), tumor specific antigens (TSAs) and damage associated molecular patterns (DAMPs), and disrupting immunosuppressive microenvironments by tumor debulking. Unfortunately, systemic administration of chemotherapeutics carries side effects of blunting anti-cancer immune response through systemic immunosuppression, which deserves to be explored as an inner contradiction in chemoimmunotherapy. Here, we proposed the hypothesis of "immunogenicity equivalence" in chemoimmunotherapy that chemotherapeutics-induced immunogenic antigens and DAMPs in vitro that can subsequently be incorporated into nanovaccines, which will possess comparable immunostimulatory potential when compared to tumors treated with systemic chemotherapy in vivo. The proteomic analysis confirmed that our nanovaccines contained TAAs, TSAs and DAMPs. Improvement in treatment outcomes in tumor-bearing mice receiving anti-PD-1 and chemotherapy-induced nanovaccines was then observed. Furthermore, we demonstrated the feasibility of replacing long-term chemotherapy with nanovaccines in chemoimmunotherapy. Our nanovaccine strategy would be a general choice for formulating cancer vaccines in personalized medicine.