CAR-T cell therapy targeting carbohydrates in cancer: SweetCAR

Programme(s): H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)

Topic(s): ERC-2020-POC - Call for proposals for ERC Proof of Concept Grant

Call for proposal: ERC-2020-PoC

Funding Scheme: ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot

Grant agreement ID: 957512

Project description:
Targeting the 'sweet tooth' of cancer
Chimeric antigen receptor T (CAR-T) cells constitute a novel immunotherapy approach against cancer. Current clinical CAR-T cells target mostly hematological tumours. However, the treatment of solid tumours has been met with limited success mainly due to the heterogeneity and poor antigenicity of the selected antigens. To overcome this problem, the EU-funded SweetCAR project proposes to develop CAR-T cells that target carbohydrate neoantigens containing sialic acid encountered in many carcinomas. Considering that cancer cells present a different glycosylation pattern from normal cells, the SweetCAR approach is expected to exhibit high specificity and safety.

Objective:
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.