Advances in the use of natural receptor- or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies

Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies. In this review, we will highlight the performance of receptor-ligand combinations as designs for CARs to treat cancer, with a particular focus on haematologic malignancies.