Journal
JCI INSIGHT
Volume 6, Issue 1, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.141502
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Funding
- amfAR ARCHE Awards [108688-54-RGRL, 108929-56-RGRL]
- California Institute of Regenerative Medicine (CIRM) Quest Discovery grant [DISC2-10748]
- James B. Pendleton Charitable Trust
- McCarthy Family Foundation
- NIH Office of Research Infrastructure Programs (ORIP) [U42OD011123, P51OD010425]
- P30 Cancer Center Support Grant through NCI [P30 CA015704]
- NIH U19 grant [AI117941, AI149504, AI126623, HL129902, U19 HL156247]
- NIH UM1 grant [AI117941, AI149504, AI126623, HL129902, U19 HL156247]
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Allogeneic hematopoietic stem cell transplantation with CCR5(-) donor cells is the only known cure for HIV-1 in patients with underlying malignancy, but is not suitable for most HIV patients due to transplant-related side effects. Chimeric antigen receptor immunotherapies may replace allo-HSCT and spread within the patient's body.
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.
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