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Chemically Programmable and Switchable CAR‐T Therapy
Author(s) -
Qi Junpeng,
Tsuji Kohei,
Hymel David,
Burke Terrence R.,
Hudecek Michael,
Rader Christoph,
Peng Haiyong
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202005432
Subject(s) - biodistribution , chimeric antigen receptor , small molecule , in vitro , antibody , in vivo , chemistry , antigen , receptor , immune system , biophysics , microbiology and biotechnology , biochemistry , t cell , biology , immunology , genetics
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.