Evaluation of chimeric antigen receptor T cell therapy in non-human primates infected with SHIV or SIV

Achieving a functional cure is an important goal in the development of HIV therapy. Eliciting HIV-specific cellular immune responses has not been sufficient to achieve durable removal of HIV-infected cells due to the restriction on effective immune responses by mutation and establishment of latent r...

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Bibliographic Details
Published in:PloS one 2021-03, Vol.16 (3), p.e0248973-e0248973
Main Authors: Iwamoto, Nami, Patel, Bhavik, Song, Kaimei, Mason, Rosemarie, Bolivar-Wagers, Sara, Bergamaschi, Cristina, Pavlakis, George N, Berger, Edward, Roederer, Mario
Format: Article
Language:English
Subjects:
Adoptive transfer
Antigens
Antiretroviral agents
Antiretroviral therapy
Biology and Life Sciences
Cancer
Cancer vaccines
CD4 antigen
Cell therapy
Chimeric antigen receptors
Chronic infection
Cloning
Data analysis
Editing
Evaluation
Experiments
Genetic aspects
HIV
Human immunodeficiency virus
Hypersensitivity
Immunology
Immunotherapy
In vivo methods and tests
Infections
Infectious diseases
Lymphocytes
Lymphocytes T
Medical research
Medicine and Health Sciences
Methodology
Monoclonal antibodies
Mutation
Public health
Research and Analysis Methods
Research facilities
Reviews
Simian immunodeficiency virus
Vaccines
Viral diseases
Viruses
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Summary:Achieving a functional cure is an important goal in the development of HIV therapy. Eliciting HIV-specific cellular immune responses has not been sufficient to achieve durable removal of HIV-infected cells due to the restriction on effective immune responses by mutation and establishment of latent reservoirs. Chimeric antigen receptor (CAR) T cells are an avenue to potentially develop more potent redirected cellular responses against infected T cells. We developed and tested a range of HIV- and SIV-specific chimeric antigen receptor (CAR) T cell reagents based on Env-binding proteins. In general, SHIV/SIV CAR T cells showed potent viral suppression in vitro, and adding additional CAR molecules in the same transduction resulted in more potent viral suppression than single CAR transduction. Importantly, the primary determinant of virus suppression potency by CAR was the accessibility to the Env epitope, and not the neutralization potency of the binding moiety. However, upon transduction of autologous T cells followed by infusion in vivo, none of these CAR T cells impacted either acquisition as a test of prevention, or viremia as a test of treatment. Our study illustrates limitations of the CAR T cells as possible antiviral therapeutics.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0248973