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TitleThe therapeutic landscape for cells engineered with chimeric antigen receptors.
Publication TypeJournal Article
Year of Publication2020
AuthorsMacKay, Matthew, Afshinnekoo Ebrahim, Rub Jonathan, Hassan Ciaran, Khunte Mihir, Baskaran Nithyashri, Owens Bryan, Liu Lauren, Roboz Gail J., Guzman Monica L., Melnick Ari M., Wu Shixiu, and Mason Christopher E.
JournalNat Biotechnol
Volume38
Issue2
Pagination233-244
Date Published2020 02
ISSN1546-1696
KeywordsCell Engineering, Cell- and Tissue-Based Therapy, Clinical Trials as Topic, Gene Expression Regulation, Neoplastic, Humans, Neoplasms, Receptors, Chimeric Antigen
Abstract

<p>Despite the global rapid increase in the number of clinical trials employing chimeric antigen receptors (CARs), no comprehensive survey of their scope, targets and design exists. In this study, we present an interactive CAR clinical trial database, spanning 64 targets deployed in T cells (CAR-T), natural killer cells (CAR-NK) or mixtures (CAR-NK/T) from over 500 clinical trials in 20 countries, encompassing >20,000 patients. By combining these data with transcriptional and proteomic data, we create a 'targetable landscape' for CAR cell therapies based on 13,206 proteins and RNAs across 78 tissues, 124 cell types and 20 cancer types. These data suggest a landscape of over 100 single targets and over 100,000 target pairs using logical switches for CAR cell engineering. Our analysis of the CAR cellular therapeutic landscape may aid the design of future therapies, improve target-to-patient matching, and ultimately help inform our understanding of CAR therapy's safety and efficacy.</p>

DOI10.1038/s41587-019-0329-2
Alternate JournalNat Biotechnol
PubMed ID31907405
Grant ListR01 MH117406 / MH / NIMH NIH HHS / United States
P01 CA214274 / CA / NCI NIH HHS / United States