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.
