@article{9991320d53d34ae88d9979c4ed7aa524,
title = "CD7 CAR T Cells for the Therapy of Acute Myeloid Leukemia",
abstract = " Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has the risk of toxicity to normal myeloid cells. CD7 is expressed by the leukemic blasts and malignant progenitor cells of approximately 30% of AML patients but is absent on normal myeloid and erythroid cells. Since CD7 expression by malignant blasts is also linked with chemoresistance and poor outcomes, targeting this antigen may be beneficial for this subset of AML patients. Here, we show that expression of a CD7-directed CAR in CD7 gene-edited (CD7 KO ) T cells effectively eliminates CD7 + AML cell lines, primary CD7 + AML, and colony-forming cells but spares myeloid and erythroid progenitor cells and their progeny. In a xenograft model, CD7 CAR T cells protect mice against systemic leukemia, prolonging survival. Our results support the feasibility of using CD7 KO CD7 CAR T cells for the non-myeloablative treatment of CD7 + AML. ",
keywords = "CAR T cells, CD7, acute myeloid leukemia, chimeric antigen receptors, mouse model",
author = "Diogo Gomes-Silva and Erden Atilla and Atilla, {Pinar Ataca} and Feiyan Mo and Haruko Tashiro and Madhuwanti Srinivasan and Premal Lulla and Rouce, {Rayne H.} and Cabral, {Joaquim M.S.} and Ramos, {Carlos A.} and Malcolm Brenner and Maksim Mamonkin",
note = "Funding Information: The authors thank Catherine Gillespie for editing the manuscript, Dimitrios Wagner, Michael Gundry, Lorenzo Brunetti for assistance with genome editing, and Stephen Gottschalk and Tim Sauer for providing the KG-1a cell line. This study was supported by a grant from the NIH National Cancer Institute (NCI) (P50 CA126752) and an American Society of Hematology (ASH) Scholar Award (to M.M.). The authors also appreciate the support of shared resources in the Dan L Duncan Comprehensive Cancer Center (support grant NCIP30CA125123 from the NIH NCI). Funding Information: The authors thank Catherine Gillespie for editing the manuscript, Dimitrios Wagner, Michael Gundry, Lorenzo Brunetti for assistance with genome editing, and Stephen Gottschalk and Tim Sauer for providing the KG-1a cell line. This study was supported by a grant from the NIH National Cancer Institute (NCI) ( P50 CA126752 ) and an American Society of Hematology (ASH) Scholar Award (to M.M.). The authors also appreciate the support of shared resources in the Dan L Duncan Comprehensive Cancer Center (support grant NCIP30CA125123 from the NIH NCI ). Publisher Copyright: {\textcopyright} 2018 The American Society of Gene and Cell Therapy Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2019",
month = jan,
day = "2",
doi = "10.1016/j.ymthe.2018.10.001",
language = "English (US)",
volume = "27",
pages = "272--280",
journal = "Molecular therapy : the journal of the American Society of Gene Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "1",
}