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

Authors: Barber-Axthelm, Isaac M.; Barber-Axthelm, Valerie; Sze, Kai Yin; Zhen, Anjie; Suryawanshi, Gajendra W.; Chen, Irvin S. Y.; Zack, Jerome A.; Kitchen, Scott G.; Kiem, Hans-Peter; Peterson, Christopher W.

Online: https://insight.jci.org/articles/view/141502

Issue: JCI Insight . 2021 Jan 11;6(1):e141502.


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.