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Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses
Name
nihms952466.pdf
Description
Accepted version
Size
2.49 MB
Format
Adobe PDF
Checksum (MD5)
c57fbdcd85e2770d5cedc92558bd3e96
Author(s)
Cho, Jang Hwan
Collins, James J
Wong, Wilson W
Date Issued
2018
Journal
Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2018 Elsevier Inc. 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. A chimeric antigen receptor system that can integrate signals from multiple antigens and fine-tune T cell activation in a cell-type-specific manner holds promise for enhancing the safety and specificity of CAR T cell therapies for cancer treatment.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1016/J.CELL.2018.03.038
