@article{651b752ec99c4b6f8c3029b48dba1dc1,
title = "CD7-deleted hematopoietic stem cells can restore immunity after CAR T cell therapy",
abstract = "Targeting T cell malignancies with universal CD7-targeting chimeric antigen receptor T cells (UCART7) can lead to profound immune deficiency due to loss of normal T and NK cells. While a small population of endogenous CD7- T cells exists, these cells are unlikely to be able to repopulate the entire immune repertoire after UCART7 treatment, as they are limited in number and proliferative capacity. To rescue T and NK cells after UCART7, we created hematopoietic stem cells genetically deleted for CD7 (CD7-KO HSCs). CD7-KO HSCs were able to engraft immunodeficient mice and differentiate into T and NK cells lacking CD7 expression. CD7-KO T and NK cells could perform effector functions as robustly as control T and NK cells. Furthermore, CD7-KO T cells were phenotypically and functionally distinct from endogenous CD7- T cells, indicating that CD7-KO T cells can supplement immune functions lacking in CD7- T cells. Mice engrafted with CD7-KO HSCs maintained T and NK cell numbers after UCART7 treatment, while these were significantly decreased in control mice. These studies support the development of CD7-KO HSCs to augment host immunity in patients with T cell malignancies after UCART7 treatment.",
author = "Kim, {Miriam Y.} and Matthew Cooper and Jacobs, {Miriam T.} and Ritchey, {Julie K.} and Julia Hollaway and Fehniger, {Todd A.} and DiPersio, {John F.}",
note = "Funding Information: We thank the Genome Engineering and iPSC core (GEiC) at Washington University School of Medicine for assistance with NGS to identify the on-target and off-target mutations generated by CRISPR/Cas9 gene editing, and the Siteman Flow Cytometry Core (SFC) for assistance with cell sorting. The long-acting recombinant human IL-7 was provided by NeoImmuneTech Inc. The graphical abstract and study schemas were created using Biorender (www.biorender.com). This study was supported by an Alex{\textquoteright}s Lemonade Stand Foundation/Northwestern Mutual Young Investigator Award (MYK); Washington University SPORE in Leukemia Career Enhancement Program (MYK); a Dean{\textquoteright}s Scholars Award from the Washington University Division of Physician-Scientists, which is funded by a Burroughs Wellcome Fund Physician-Scientist Institutional Award (MYK); NCI/NIH P50 CA171963 Leukemia SPORE (JFD); NCI/NIH: R35 CA210084 NCI Outstanding Investigation Award (JFD); and NCI/NIH: Genomics of AML P01 CA101937 (JFD). Publisher Copyright: {\textcopyright} 2021, Kim et al.",
year = "2021",
month = aug,
day = "23",
doi = "10.1172/jci.insight.149819",
language = "English",
volume = "6",
journal = "JCI insight",
issn = "2379-3708",
number = "16",
}