Abstract
Abstract Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has shown great promise in harnessing host immune system to combat cancer. That said, only a portion of patients has benefit directly from the anti–programmed cell death protein 1 (anti-PD1) therapy, whereas the others with an immunosuppressive tumor microenvironment (TME) achieve poor clinical outcomes. Hence, promoting an immune-stimulating TME that favors tumor-infiltrating lymphocytes is an important means to maximize the cancer immunotherapeutic potentials. Small-molecule prodrugs conferred intratumoral delivery of ICI agents have emerged as novel local delivery approaches to enhance antitumor immunity for cancer therapy. Our recent study revealed a combined chemoimmunotherapy could serve as a reservoir for extended release of DNA-damaging agent camptothecin and ICI agent anti-PD1 antibody, thus eliciting robust and durable systemic antitumor immunity in mice. The underlying mechanisms on how this carrier-free therapeutic system boosts immune sensing of immunogenic tumors and priming of CD8+ T cells against tumor antigens and the impact of microbiota will be discussed. Together, these results provide important insights into the use of small-molecule prodrugs as both chemotherapeutic and carrier, to awaken and enhance antitumor immune system for improved cancer therapy. Supported by NIH grant R01CA244350
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