(447c) Localized Delivery of Tumor-Specific Antigen and Immune Checkpoint Antibodies to Induce Systemic Antitumor Immunity

The development of cancer immunotherapeutics to enhance anti-tumor immune responses has led to significant clinical advances. However, the rate of complete response to single immunotherapy drugs remains low, due in part to the complex immune network of the tumor microenvironment. Combinations of immunotherapies improve the efficacy but result in exacerbating toxicities. None of the current delivery strategies, including local administration that still leaks potent drugs to the circulation, can avoid debilitating toxicities that prevent immunotherapies from reaching their full curative potential. To overcome such delivery problems, we developed a localized drug delivery platform using tumor antigens and immune-checkpoint antibodies with prolonged intratumoral retention to enable sustainable delivery of combinations of immunotherapeutics and elicit durable antitumor immune responses. This was supported by our preliminary studies that intratumorally administered OVA antigen and anti-PD1 significantly delayed mouse lymphoma EG7-OVA tumor outgrowth without exacerbating toxicity, compared with the local treatment of individual drugs. Additionally, we also demonstrated that the sustainable intratumoral delivery of immune checkpoint antibodies and OVA antigens could elicit durable anti-tumor responses with robust immune memories in such tumor models. We therefore envision that high efficacy and high safety can be achieved together using such localized delivery technology that allows for specific tumor eradication without systemic toxicities.