Incorporation of bacterial immunoevasins to protect cell therapies from host antibody-mediated immune rejection.
CAR T cells
IdeS
anti-CAR IgG
cell therapies
humoral response
immunogenicity
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
29
03
2021
revised:
27
05
2021
accepted:
25
06
2021
pubmed:
5
7
2021
medline:
8
4
2022
entrez:
4
7
2021
Statut:
ppublish
Résumé
Cellular therapies are engineered using foreign and synthetic protein sequences, such as chimeric antigen receptors (CARs). The frequently observed humoral responses to CAR T cells result in rapid clearance, especially after re-infusions. There is an unmet need to protect engineered cells from host-versus-graft rejection, particularly for the advancement of allogeneic cell therapies. Here, utilizing the immunoglobulin G (IgG) protease "IdeS," we programmed CAR T cells to defeat humoral immune attacks. IdeS cleavage of host IgG averted Fc-dependent phagocytosis and lysis, and the residual F(ab')
Identifiants
pubmed: 34217891
pii: S1525-0016(21)00352-X
doi: 10.1016/j.ymthe.2021.06.022
pmc: PMC8636170
pii:
doi:
Substances chimiques
Immunoglobulin G
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3398-3409Subventions
Organisme : NCI NIH HHS
ID : R01 CA055349
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA241894
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA023766
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA241400
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA239511
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA254331
Pays : United States
Informations de copyright
Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests MSKCC has filed for patent protection for D.A.S., M.M.D., and L.P. for work related to this paper. D.A.S. has an equity interest in, consults for, or is on the Board of Sellas Life Sciences, Pfizer, Oncopep, Actinium, Co-Immune, Eureka, Repertoire, Sapience, Iovance, and Arvinas. J.H.P. receives funding from the Conquer Cancer Foundation of ASCO, a Leukemia and Lymphoma Society Career Development Grant, the Geoffrey Beene Cancer Foundation, a National Comprehensive Cancer Center Young Investigator Award, and an American Society of Hematology Scholar Junior Faculty Award. J.H.P. has consulted and provided an advisory role for Amgen, Novartis, Kite Pharma, Incyte, Allogene, Autolus, Intellia, Artiva, AstraZeneca, Pfizer, Takeda, and Servier. E.L.S. received funding from NCI K08 CA241400-02. E.L.S. has licensed patents and royalties with BMS, as well as consulting and receiving research funding. E.L.S. has consulted for Fate Therapeutics and Chimeric Therapeutics.
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