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

Adoptive immunotherapy with chimeric antigen receptors (CARs) is a promising cancer treatment. CARs combine an antibody fragment recognizing cancer cells with intracellular domains triggering cytotoxic activity. However, suitable antigens or monoclonal antibodies are often lacking. Our study explores alternative ligand-receptor interactions beyond antigen-antibody binding. Since cancer cells show altered glycosylation, we investigated the glyco-profile of AML cells and patient samples using recombinant human lectin domains. Detection of glycan ligands in healthy tissue sections was performed, revealing the distribution and expression patterns to assess their potential relevance regarding toxic side effects. Based on these findings, we developed CAR constructs targeting AML and demonstrated specific cytotoxicity. We also tested a SynNotch system to enhance specificity and safety through a two-step T cell activation. Our novel CAR approach offers advantages over traditional CARs, including greater versatility, faster development, and reduced immunogenicity, expanding treatment options for cancers lacking antibody-based CAR targets.

Publication History

Article published online:
09 May 2025