Project 463187

Immune checkpoint blockade (ICB) is a new type of cancer therapy that works by strengthening immune systems to attack tumor cells. Several ICB drugs have been approved for treating solid cancers and have shown encouraging outcomes in some cancer patients. However, challenges associated with ICB still exist, including low response rates in patients and severe side effects. Therefore, engineering strategies to address these unmet clinical challenges to improve impact of current and future immunotherapies are highly needed. In this proposal, we will engineer a novel injectable hydrogel system, which we termed "cold atmospheric plasma (CAP)-preserved hydrogel (CAP-gel)", to deliver ICB drugs for enhancing ICB therapy and reducing side effects. CAP in the hydrogel is a unique type of gas that has strong anti-cancer effects and that can effectively improve the efficacy of ICB therapy. Injectable hydrogels also offer local and sustainable drug release to reduce systemic toxicities associated with ICB. We will investigate this strategy for treating triple negative breast cancer (TNBC), an aggressive type of breast cancer that has a high mortality rate among breast cancer patients. While ICB shows some positive effects in a small number of TNBC patients, the overall efficacy requires improvement and unwanted side effects need to be eliminated. Therefore, in this proposal, we aim to engineer an injectable hydrogel containing both CAP and ICB drugs to treat TNBC. We will investigate the engineered gels in treating primary TNBC and metastatic diseases. We will also evaluate the engineered gels in preventing tumor relapse. We anticipate that this treatment strategy can be easily modified and further extended to treat other solid cancers, advancing research and translation of biomaterials-mediated cancer immunotherapies, which could ultimately bring immense clinical benefits for cancer patients.