| Institution: | 1. Department of Immunology and Microbiology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL, 33458 USA;2. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 376 Boyles Street, Frederick, MD, 21702 USA
Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062 Japan;3. Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 376 Boyles Street, Frederick, MD, 21702 USA;4. Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Oberdürrbacherstrasse 6, 97080 Würzburg, Germany |
| Abstract: | Although macromolecules on cell surfaces are predominantly targeted and drugged with antibodies, they harbor pockets that are only accessible to small molecules and constitutes a rich subset of binding sites with immense potential diagnostic and therapeutic utility. Compared to antibodies, however, small molecules are disadvantaged by a less confined biodistribution, shorter circulatory half-life, and inability to communicate with the immune system. Presented herein is a method that endows small molecules with the ability to recruit and activate chimeric antigen receptor T cells (CAR-Ts). It is based on a CAR-T platform that uses a chemically programmed antibody fragment (cp-Fab) as on/off switch. In proof-of-concept studies, this cp-Fab/CAR-T system targeting folate binding proteins on the cell surface mediated potent and specific eradication of folate-receptor-expressing cancer cells in vitro and in vivo. |
