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使用可改造的CAR-T细胞进犯潜伏的艾滋病毒，这一效果由美国格拉德斯通病毒和免疫研究所Warner C. Greene课题组近来取得。相关论文10月24日在线发表于世界学术期刊《细胞》。
研究人员设计了一种根据细胞毒性T淋巴细胞（CTL）的通用CAR-T细胞渠道，其旨在结合多种广泛中和的抗HIV抗体。研究人员证明，这个渠道（即可改造的CAR-T细胞）能够仅在装备了抗HIV抗体的情况下有效地杀死血液、扁桃体或脾脏中被HIV感染的CD4 T细胞，但不影响未被感染的细胞。在抗逆转录病毒疗法的效果下，可改造的CAR-T细胞还能在48小时内杀死在HIV感染者的血液中发现的一半以上的储存库。
可改造的CAR-T细胞体系的模块性能够与多种抗HIV抗体一起运用，然后产生更大的规划和控制力，这使其有望成为进犯潜在HIV病毒库的东西。
据了解，现在减少潜在HIV储存库的办法需要首先从头激活含病毒的细胞，使其对免疫体系可见。关键的第二步是杀死这些细胞以减小储存库的大小。内源性CTL或许由于细胞衰竭和抗CTL病毒的进化而缺少。
附：英文原文
Title: Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform
Author: Eytan Herzig, Kaman Chan Kim, Thomas A. Packard, Noam Vardi, Roland Schwarzer, Andrea Gramatica, Steven G. Deeks, Steven R. Williams, Kyle Landgraf, Nigel Killeen, David W. Martin, Leor S. Weinberger, Warner C. Greene
Issue&Volume: 2019/10/24
Abstract: Current approaches to reducing the latent HIV reservoir entail first reactivating virus-containing cells to become visible to the immune system. A critical second step is killing these cells to reduce reservoir size. Endogenous cytotoxic T-lymphocytes (CTLs) may not be adequate because of cellular exhaustion and the evolution of CTL-resistant viruses. We have designed a universal CAR-T cell platform based on CTLs engineered to bind a variety of broadly neutralizing anti-HIV antibodies. We show that this platform, convertibleCAR-T cells, effectively kills HIV-infected, but not uninfected, CD4 T cells from blood, tonsil, or spleen and only when armed with anti-HIV antibodies. convertibleCAR-T cells also kill within 48 h more than half of the inducible reservoir found in blood of HIV-infected individuals on antiretroviral therapy. The modularity of convertibleCAR-T cell system, which allows multiplexing with several anti-HIV antibodies yielding greater breadth and control, makes it a promising tool for attacking the latent HIV reservoir.
DOI: 10.1016/j.cell.2019.10.002
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31118-3
