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Engineering primary T cells with chimeric antigen receptors for rewired responses to soluble ligands.
- Source :
-
Nature protocols [Nat Protoc] 2020 Apr; Vol. 15 (4), pp. 1507-1524. Date of Electronic Publication: 2020 Feb 26. - Publication Year :
- 2020
-
Abstract
- The expression of synthetic receptors in primary T cells enables the programming of user-defined responses when designing T-cell therapies. Chimeric antigen receptors (CARs) are synthetic receptors that have demonstrated efficacy in cancer therapy by targeting immobilized antigens on the surface of malignant cells. Recently, we showed they can also rewire T-cell responses to soluble ligands. In contrast to other synthetic receptors, CARs are not only readily engineered by rational design, but also clinically translatable, with robust function in primary human T cells. This protocol discusses design principles for CARs responsive to soluble ligands and delineates steps for producing T cells expressing synthetic receptors. Functional assays for quantifying the ability of CAR T cells to sense and respond to soluble ligands are also presented. This protocol provides a framework for proficient immune-cell researchers to test novel T-cell therapies targeting soluble ligands in <2 weeks.
Details
- Language :
- English
- ISSN :
- 1750-2799
- Volume :
- 15
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature protocols
- Publication Type :
- Academic Journal
- Accession number :
- 32103205
- Full Text :
- https://doi.org/10.1038/s41596-020-0294-8