Chemically Programmable and Switchable CAR-T Therapy.
CAR-Ts
antibodies
antitumor agents
cell-surface receptors
immunotherapy
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
13 07 2020
13 07 2020
Historique:
received:
14
04
2020
pubmed:
25
4
2020
medline:
26
3
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32329959
doi: 10.1002/anie.202005432
pmc: PMC7429910
mid: NIHMS1617513
doi:
Substances chimiques
Antigens, Neoplasm
0
Folate Receptor 2
0
Receptors, Antigen, T-Cell
0
Receptors, Cell Surface
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
12178-12185Subventions
Organisme : NCI NIH HHS
ID : R01 CA204484
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA174844
Pays : United States
Organisme : NIH HHS
ID : Intramural Research Program
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA181258
Pays : United States
Informations de copyright
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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