Abstract
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.
Highlights
Hematopoietic stem and progenitor cell (HSPC) transplantation has emerged as a promising approach to achieve a functional HIV cure, largely due to the clinical cases of the Berlin Patient and the London Patient [1, 2]
Necropsy samples from this cohort were, well suited to build and validate an assay to quantify the trafficking of CD4CAR+ cells, which was the main objective of this work
Our results show that CD4CAR modification of germinal centers (GCs) B cells does not hinder proliferative responses, with the relative abundance of Ki-67+ GC B cells likely reflecting lymphoid hyperplasia associated with chronic simian/human immunodeficiency virus (SHIV) infection
Summary
Hematopoietic stem and progenitor cell (HSPC) transplantation has emerged as a promising approach to achieve a functional HIV cure, largely due to the clinical cases of the Berlin Patient and the London Patient [1, 2]. While the successful treatment of these 2 patients marks a significant milestone in efforts aimed at an HIV cure, there are several limitations that render this approach infeasible for the vast majority of people living with HIV. These include significant risk of morbidity and mortality associated with allo-HSCT, the limited prevalence of CCR5Δ32 donors, and the potential for the virus to circumvent the CCR5Δ32 mutation via a CCR5- to CXCR4-tropism shift [4]. We are interested in applying principles from the successful treatment of the Berlin and London patients, using alternative approaches that are comparably potent, less toxic, and applicable to a larger patient population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
