CAR-T cell therapy targeting carbohydrates in cancer

ended

Major limitations in current immunotherapy success are low antigenicity of targeting antigen and tumor heterogeneity. Hence there is an unmet need for novel antigen targets that could potentially be expressed on many tumor types. Cancer express aberrant cell surface glycosylation patterns compared to normal cells. These tumor-associated carbohydrate-neoantigens can be targeted for tumor cell killing by antibodies and cytotoxic immune cells. Sialic acids cover cell surface glycans and frequently have altered expression on many types of carcinoma cells and correlate with cancer progression and/or metastasis. We aim to focus on targeting sialic acid containing carbohydrate-neoantigens using the chimeric antigen receptor T cell (CAR-T) immunotherapy approach. Current clinical CAR-T cells target mostly soluble tumors using CD19, BCMA and other non-cancer specific antigens that often suffer toxicity and side effects. Our universal anti-carbohydrate CAR-T approach could target many types of carcinomas with high specificity and safety, and could potentially reach patients rapidly.