A computationally designed chimeric antigen receptor provides a small-molecule safety switch for T-cell therapy

Journal:
Nature Biotechnology
Published:
DOI:
10.1038/s41587-019-0403-9
Affiliations:
6
Authors:
15
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Research Highlight

A stop switch for cancer cell therapy

© Grafissimo/Getty

A new type of molecular emergency brake could help improve the safety of cellular immunotherapies for cancer patients.

T cells engineered with tumour-targeting constructs known as chimeric antigen receptors (CARs) offer a potent way to supercharge the immune system against cancer. But the therapies carry a risk of runaway immune responses against healthy tissues.

A team that included scientists from the Korea Advanced Institute of Science and Technology (KAIST) has now designed CAR T cells that can be reversibly inactivated with drugs.

The researchers split the conventional CAR construct in two and introduced a linker chain made of interacting domains that spontaneously come together inside the cell to promote T cell activation, but are kept apart in the presence of certain small-molecule drugs.

The researchers validated their system in human prostate-cancer cells and in a mouse model of the disease.

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References

  1. Nature Biotechnology 38, 426–432 (2020). doi: 10.1038/s41587-019-0403-9
Institutions Authors Share
University of Lausanne (UNIL), Switzerland
3.500000
 0.23
University Hospital of Lausanne (CHUV), UNIL, Switzerland
3.500000
 0.23
Korea Advanced Institute of Science and Technology (KAIST), South Korea
3.000000
 0.20
Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland
2.500000
 0.17
Swiss Institute of Bioinformatics (SIB), Switzerland
2.500000
 0.17