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利用可改造CAR-T系统或可消灭潜伏HIV
作者:小柯机器人 发布时间:2019/10/25 16:14:49

利用可改造的CAR-T细胞攻击潜伏的艾滋病毒,这一成果由美国格拉德斯通病毒和免疫研究所Warner C. Greene课题组近日取得。相关论文10月24日在线发表于国际学术期刊《细胞》。

研究人员设计了一种基于细胞毒性T淋巴细胞(CTL)的通用CAR-T细胞平台,其旨在结合多种广泛中和的抗HIV抗体。研究人员证明,这个平台(即可改造的CAR-T细胞)可以仅在配备了抗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作用下,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细胞系统的模块性可以与多种抗HIV抗体同时使用,从而产生更大的范围和控制力,这使其有望成为攻击潜在HIV病毒库的工具。

据了解,目前减少潜在HIV储存库的方法需要首先重新激活含病毒的细胞,使其对免疫系统可见。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可能由于细胞衰竭和抗CTL病毒的进化而不足。

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

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/