Stem cell-derived CAR T cells traffic to HIV reservoirs in macaques

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with CCR5- donor cells is the only treatment known to cure HIV-1 in patients with underlying malignancy. This is likely due to a donor cell-mediated graft-versus-host effect targeting HIV reservoirs. Allo-HSCT would not be an acceptable...

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Veröffentlicht in:JCI insight 2021-01, Vol.6 (1)
Hauptverfasser: Barber-Axthelm, Isaac M, Barber-Axthelm, Valerie, Sze, Kai Yin, Zhen, Anjie, Suryawanshi, Gajendra W, Chen, Irvin Sy, Zack, Jerome A, Kitchen, Scott G, Kiem, Hans-Peter, Peterson, Christopher W
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Sprache:eng
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Zusammenfassung:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with CCR5- donor cells is the only treatment known to cure HIV-1 in patients with underlying malignancy. This is likely due to a donor cell-mediated graft-versus-host effect targeting HIV reservoirs. Allo-HSCT would not be an acceptable therapy for most people living with HIV due to the transplant-related side effects. Chimeric antigen receptor (CAR) immunotherapies specifically traffic to malignant lymphoid tissues (lymphomas) and, in some settings, are able to replace allo-HSCT. Here, we quantified the engraftment of HSC-derived, virus-directed CAR T cells within HIV reservoirs in a macaque model of HIV infection, using potentially novel IHC assays. HSC-derived CAR cells trafficked to and displayed multilineage engraftment within tissue-associated viral reservoirs, persisting for nearly 2 years in lymphoid germinal centers, the brain, and the gastrointestinal tract. Our findings demonstrate that HSC-derived CAR+ cells reside long-term and proliferate in numerous tissues relevant for HIV infection and cancer.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.141502