Chemically Programmable and Switchable CAR-T Therapy

Qi J, Tsuji K, Hymel D, Burke TR, Hudecek M, Rader C, Peng H (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Angewandte Chemie International Edition Wiley

Book Volume: 59

Pages Range: 12178-12185

Journal Issue: 29

DOI: 10.1002/anie.202005432

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.

Involved external institutions

Scripps Research Institute (TSRI) US United States (USA) (US) National Cancer Institute (NCI) US United States (USA) (US) Universitätsklinikum Würzburg DE Germany (DE)

How to cite

APA:

Qi, J., Tsuji, K., Hymel, D., Burke, T.R., Hudecek, M., Rader, C., & Peng, H. (2020). Chemically Programmable and Switchable CAR-T Therapy. Angewandte Chemie International Edition, 59(29), 12178-12185. https://doi.org/10.1002/anie.202005432

MLA:

Qi, Junpeng, et al. "Chemically Programmable and Switchable CAR-T Therapy." Angewandte Chemie International Edition 59.29 (2020): 12178-12185.

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