ABSTRACT T cell malignancies represent a group of hematologic cancers with high rates of relapse and mortality in patients for whom no effective targeted therapies exist. The shared

expression of target antigens between chimeric antigen receptor (CAR) T cells and malignant T cells has limited the development of CAR-T because of unintended CAR-T fratricide and an

inability to harvest sufficient autologous T cells. Here, we describe a fratricide-resistant “off-the-shelf” CAR-T (or UCART7) that targets CD7+ T cell malignancies and, through CRISPR/Cas9

gene editing, lacks both CD7 and T cell receptor alpha chain (TRAC) expression. UCART7 demonstrates efficacy against human T cell acute lymphoblastic leukemia (T-ALL) cell lines and primary

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CD7 TARGETED “OFF-THE-SHELF” CAR-T DEMONSTRATES ROBUST IN VIVO

EXPANSION AND HIGH EFFICACY IN THE TREATMENT OF PATIENTS WITH RELAPSED AND REFRACTORY T CELL MALIGNANCIES Article 12 September 2023 AN “OFF-THE-SHELF” CD2 UNIVERSAL CAR-T THERAPY FOR T-CELL

MALIGNANCIES Article Open access 05 October 2023 TRBC1-CAR T CELL THERAPY IN PERIPHERAL T CELL LYMPHOMA: A PHASE 1/2 TRIAL Article Open access 11 November 2024 REFERENCES * Ma H, Abdul-Hay

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Blood. 1996;8:3230–9. Google Scholar  Download references ACKNOWLEDGEMENTS This work is dedicated in memory of Gordon S. Cooper. 1946–2017. We thank Dr. Carl June (University of

Pennsylvania) for providing the backbone of a third-generation CAR and the pELNS-Ef1α lentiviral vector. FUNDING Specialized Program of Research Excellence (SPORE) in Leukemia NIH:

1P50CA171063-01A1, R35 CA210084-01A, the Gabrielle’s Angels Foundation, the Children's Discovery Institute of Washington University and St. Louis Children's Hospital, the Alvin J.

Siteman Cancer Research Fund at Washington University in St. Louis, MO. AUTHOR CONTRIBUTIONS MLC and JFD conceived project. MLC, JFD, JC, and MR designed the experiments. MLC, JKR, JMN, and

KE cloned the CAR constructs and generated virus. MLC performed gene editing and generated CAR-T. MLC, JKR, and JO preformed and analyzed in vitro assays. MLC, JKR, JMN, BW, and LNG

performed in vivo experiments. JLP and SA performed BLI imaging. KS and MLC performed FACS analysis. DMW and AG developed PDX models. MLC, CAM, CCF, and RSF completed and analyzed off-target

nuclease activity analysis. FG performed all statistical analyses. All authors were involved in the interpretation of data and preparation of this manuscript. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, 63110, USA Matthew L Cooper, Jaebok Choi, Karl Staser, Julie K

Ritchey, Jessica M Devenport, Kayla Eckardt, Michael P Rettig, Bing Wang, Linda G Eissenberg, Armin Ghobadi, Leah N Gehrs, Christopher A Miller, Julie O’Neal & John F DiPersio *

Department of Internal Medicine, Division of Dermatology, Washington University School of Medicine, St. Louis, MO, 63110, USA Karl Staser * Mallinckrodt Institute of Radiology, Washington

University in St. Louis School of Medicine, St. Louis, MO, 63110, USA Julie L Prior & Samuel Achilefu * McDonnell Genome Institute, Washington University School of Medicine, St. Louis,

MO, 63108, USA Christopher A Miller, Catrina C Fronick & Robert S Fulton * Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis,

MO, 63110, USA Feng Gao * Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA David M Weinstock & Alejandro Gutierrez * Division of Hematology/Oncology,

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AUTHORS Correspondence to Matthew L Cooper or John F DiPersio. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ELECTRONIC SUPPLEMENTARY

MATERIAL SUPPLEMENTAL MATERIAL RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Cooper, M.L., Choi, J., Staser, K. _et al._ An “off-the-shelf”

fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. _Leukemia_ 32, 1970–1983 (2018). https://doi.org/10.1038/s41375-018-0065-5 Download citation * Received: 18

December 2017 * Revised: 22 January 2018 * Accepted: 01 February 2018 * Published: 20 February 2018 * Issue Date: September 2018 * DOI: https://doi.org/10.1038/s41375-018-0065-5 SHARE THIS

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