Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy.

Journal: Immunity

Published: 2020-08-18

DOI: 10.1016/j.immuni.2020.07.011

Affiliations: 10

Authors: 15

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Research Highlight

CAR trafficking improved

© KEITH CHAMBERS/SCIENCE PHOTO LIBRARY/Getty

© KEITH CHAMBERS/SCIENCE PHOTO LIBRARY/Getty

A new way of engineering T cells to selectively attack tumours makes boosts the anti-cancer activity of these therapeutic cells in mice and also makes them last longer.

A team co-led by scientists at ShanghaiTech University showed that chimeric antigen receptors (CARs) — constructs designed to redirect the immune responses of cells to proteins expressed by tumours — regularly traffic from the outside of resting T cells, to the inside, and back to the surface again.

However, the long-term cancer-fighting ability of CAR-bearing T cells is limited because when they engage their targets on tumour cells, they get tagged for destruction. To prevent this from happening, the researchers mutated parts of the CAR. When added to T cells, the resulting ‘recyclable CAR’ proved more durable in tumour-bearing mice than standard CARs.

The same concept could enhance the persistence and functionality of CAR-bearing T cells used clinically for treating patients.

Supported content

  1. Immunity 53, 456–470 (2020). doi: doi: 10.1016/j.immuni.2020.07.011
Institutions Share
ShanghaiTech University, China 0.26
Eye and Ear, Nose, and Throat Hospital, Fudan University, China 0.20
Southern University of Science and Technology (SUSTech), China 0.13
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.11
CAS Center for Excellence in Molecular Cell Science, SIBS CAS, China 0.11
Academy for Advanced Interdisciplinary Studies (AAIS), PKU, China 0.07
Center for Life Sciences (CLS), PKU, China 0.07
University of Chinese Academy of Sciences (UCAS), China 0.05

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