Journal
CELL
Volume 173, Issue 6, Pages 1426-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.03.038
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Funding
- Kwanjeong Educational Foundation
- Paul G. Allen Frontiers Group
- Wyss Institute
- Boston University
- NIH Director's New Innovator Award [1DP2CA186574]
- NSF Expedition in Computing [1522074]
- NSF CAREER [162457]
- NSF BBSRC [1614642]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1614642] Funding Source: National Science Foundation
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T cells expressing chimeric antigen receptors (CARs) are promising cancer therapeutic agents, with the prospect of becoming the ultimate smart cancer therapeutics. To expand the capability of CAR T cells, here, we present a split, universal, and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical upgrades, such as the ability to switch targets without re-engineering the T cells, finely tune T cell activation strength, and sense and logically respond to multiple antigens. These features are useful to combat relapse, mitigate over-activation, and enhance specificity. We test our SUPRA system against two different tumor models to demonstrate its broad utility and humanize its components to minimize potential immunogenicity concerns. Furthermore, we extend the orthogonal SUPRA CAR system to regulate different T cell subsets independently, demonstrating a dually inducible CAR system. Together, these SUPRA CARs illustrate that multiple advanced logic and control features can be implemented into a single, integrated system.
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