Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Comparative Medicine, University of Washington, Seattle, Washington, USA.
JCI Insight. 2021 Jan 11;6(1):141502. doi: 10.1172/jci.insight.141502.
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.
异基因造血干细胞移植（allo-HSCT）使用 CCR5-供体细胞是已知的唯一能够治愈患有潜在恶性肿瘤的 HIV-1 患者的方法。这可能是由于供体细胞介导的移植物抗宿主效应针对 HIV 储存库。由于移植相关的副作用，allo-HSCT 不太可能成为大多数 HIV 感染者的可接受治疗方法。嵌合抗原受体（CAR）免疫疗法专门针对恶性淋巴组织（淋巴瘤），并且在某些情况下能够替代 allo-HSCT。在这里，我们使用潜在的新型免疫组织化学检测方法，在 HIV 感染的猕猴模型中定量评估源自 HSC 的、针对病毒的 CAR T 细胞在 HIV 储存库中的植入情况。源自 HSC 的 CAR 细胞在与组织相关的病毒储存库中迁移并显示多谱系植入，在淋巴生发中心、大脑和胃肠道中持续存在近 2 年。我们的研究结果表明，源自 HSC 的 CAR+细胞在与 HIV 感染和癌症相关的许多组织中长期存在并增殖。
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