Glyco-binding domain chimeric antigen receptors as a new option for cancer immunotherapy

A conventionel CAR consists of an antibody fragment designed to specifically recognize target structures on cancer cells and intracellular signaling domains. For many cancer entities, a suitable antigen is missing or no monoclonal antibody is available for the construction of a CAR. We show that, lectin-glycan interactions are suitable for use in immunotherapy. Cancer cells are often characterized by an altered glycosylation pattern, which can be recognized by lectins. Replacing the antibody fragment with the glyco-binding domain of a human lectins in a CAR construct leads to targeted cancer cell killing. Using the glycan-binding properties of the CD301 receptor, we have developed a novel type of CAR (LEC-CAR) that enables cytotoxic effector cells to recognize Tn and sialyl-Tn antigens and thus eliminate cancer cells. In addition, we investigated the glycosylation profile of acute myeloid leukemia (AML) cell lines and patient material. Based on this, we developed more CAR constructs to target this cancer entity and could show a specific killing in vitro. Our novel LEC-CAR concept offers several advantages: broader applicability, short generation time, and low immunogenicity.

Publication History

Article published online:
10 May 2024