Journal article
Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function
- Abstract:
- T cells engineered to express chimeric antigen receptors (CAR-T cells) have shown impressive clinical efficacy in the treatment of B cell malignancies. However, the development of CAR-T cell therapies for solid tumors is hampered by the lack of truly tumor-specific antigens and poor control over T cell activity. Here we present an avidity-controlled CAR (AvidCAR) platform with inducible and logic control functions. The key is the combination of (i) an improved CAR design which enables controlled CAR dimerization and (ii) a significant reduction of antigen-binding affinities to introduce dependence on bivalent interaction, i.e. avidity. The potential and versatility of the AvidCAR platform is exemplified by designing ON-switch CARs, which can be regulated with a clinically applied drug, and AND-gate CARs specifically recognizing combinations of two antigens. Thus, we expect that AvidCARs will be a highly valuable platform for the development of controllable CAR therapies with improved tumor specificity.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.6MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-020-17970-3
Authors
- Publisher:
- Nature Research
- Journal:
- Nature communications More from this journal
- Volume:
- 11
- Pages:
- 1-15
- Article number:
- ARTN 4166
- Place of publication:
- England
- Publication date:
- 2020-08-20
- Acceptance date:
- 2020-07-23
- DOI:
- EISSN:
-
2041-1723
- ISSN:
-
2041-1723
- Pmid:
-
32820173
- Language:
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English
- Keywords:
- Pubs id:
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1127743
- Local pid:
-
pubs:1127743
- Deposit date:
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2020-10-20
- ARK identifier:
Terms of use
- Copyright holder:
- The Author (s)
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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