HIV-Specific CAR T Cells with CD28 or 4-1BB Signaling Domains Are Phenotypically and Functionally Distinct and Effective at Suppressing HIV and Simian Immunodeficiency Virus.

Autor:	Cartwright EK; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN; ekcartwright@gmail.com skinn002@umn.edu., Pampusch MS; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN., Rendahl AK; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN., Berger EA; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and., Coleman-Fuller N; MarPam Pharma LLC, Saint Paul, MN., Skinner PJ; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN; ekcartwright@gmail.com skinn002@umn.edu.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2022 Oct 11; Vol. 6 (10), pp. 693-704. Date of Electronic Publication: 2022 Oct 11.
DOI:	10.4049/immunohorizons.2200073
Abstrakt:	Despite mounting a robust antiviral CD8 T cell response to HIV infection, most infected individuals are unable to control HIV viral load without antiretroviral therapy (ART). Chimeric Ag receptor (CAR) T cell treatment is under intensive investigation as an alternative therapy for ART-free remission of chronic HIV infection. However, achieving durable remission of HIV will require a successful balance between CAR T cell effector function and persistence. CAR T cells with CD28 costimulatory domains have robust effector function but limited persistence in vivo, whereas CAR T cells with 4-1BB costimulatory domains present a more undifferentiated phenotype and greater in vivo persistence. We compared the in vitro phenotype and function of rhesus macaque and human CAR T cells that contained either the CD28 or 4-1BB costimulatory domain; both constructs also included CARs that are bispecific for gp120 of HIV or SIV and the CXCR5 moiety to promote in vivo homing of CAR/CXCR5 T cells to B cell follicles. Cells were transduced using a gammaretroviral vector and evaluated using flow cytometry. 4-1BB-CAR/CXCR5 T cells were phenotypically distinct from CD28-CAR/CXCR5 T cells and showed increased expression of CAR and CD95. Importantly, both CD28- and 4-1BB-CAR/CXCR5 T cells retained equal capacity to recognize and suppress SIV in vitro. These studies provide new insights into rhesus macaque and human 4-1BB- and CD28-bearing CAR T cells. (Copyright © 2022 The Authors.)
Databáze:	MEDLINE
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