Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Cho JH,Collins JJ,Wong WWdoi
10.1016/j.cell.2018.03.038subject
Has Abstractpub_date
2018-05-31 00:00:00pages
1426-1438.e11issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30362-3journal_volume
173pub_type
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