CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection.

Autor: Pampusch MS; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Abdelaal HM; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Cartwright EK; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Molden JS; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Davey BC; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Sauve JD; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Sevcik EN; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Rendahl AK; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America., Rakasz EG; Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin, United States of America., Connick E; Division of Infectious Diseases, University of Arizona, Tucson, Arizona, United States of America., Berger EA; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, Maryland, United States of America., Skinner PJ; Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Feb 07; Vol. 18 (2), pp. e1009831. Date of Electronic Publication: 2022 Feb 07 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1009831
Abstrakt: During chronic human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles of secondary lymphoid tissues. We investigated whether infusion of T cells expressing an SIV-specific chimeric antigen receptor (CAR) and the follicular homing receptor, CXCR5, could successfully kill viral-RNA+ cells in targeted lymphoid follicles in SIV-infected rhesus macaques. In this study, CD4 and CD8 T cells from rhesus macaques were genetically modified to express antiviral CAR and CXCR5 moieties (generating CAR/CXCR5-T cells) and autologously infused into a chronically infected animal. At 2 days post-treatment, the CAR/CXCR5-T cells were located primarily in spleen and lymph nodes both inside and outside of lymphoid follicles. Few CAR/CXCR5-T cells were detected in the ileum, rectum, and lung, and no cells were detected in the bone marrow, liver, or brain. Within follicles, CAR/CXCR5-T cells were found in direct contact with SIV-viral RNA+ cells. We next infused CAR/CXCR5-T cells into ART-suppressed SIV-infected rhesus macaques, in which the animals were released from ART at the time of infusion. These CAR/CXCR5-T cells replicated in vivo within both the extrafollicular and follicular regions of lymph nodes and accumulated within lymphoid follicles. CAR/CXR5-T cell concentrations in follicles peaked during the first week post-infusion but declined to undetectable levels after 2 to 4 weeks. Overall, CAR/CXCR5-T cell-treated animals maintained lower viral loads and follicular viral RNA levels than untreated control animals, and no outstanding adverse reactions were noted. These findings indicate that CAR/CXCR5-T cell treatment is safe and holds promise as a future treatment for the durable remission of HIV.
Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: Pamela Skinner is the co-founder and CSO of MarPam Pharma and has a patent pending US20180371057A1. Mary Pampusch was a former employee of MarPam Pharma. Other authors declare that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje