A Universal CAR-NK Cell Targeting Various Epitopes of HIV-1 gp160.
A Universal CAR-NK Cell Targeting Various Epitopes of HIV-1 gp160.
复制标题
DOI：
10.1021/acschembio.0c00537
复制
发表时间：
2020-08-21
影响因子：
4
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Lim RM;Rong L;Zhen A;Xie J
用抗HIV嵌合抗原受体（CAR）工程化T细胞和自然杀伤（NK）细胞已经成为根除HIV感染细胞的有希望的策略。然而，目前的抗HIV汽车受到靶向HIV包膜糖蛋白gp 160的单个表位的限制，这无法对抗病毒的巨大多样性和可变性。在这里，我们报告了一种通用CAR-NK细胞的开发，该细胞识别2，4-二硝基苯基（DNP），随后可以使用DNP缀合的抗体作为衔接分子重定向到靶向gp 160的各种表位。我们发现这种CAR-NK细胞可以识别和杀死表达亚型B和C gp 160的模拟HIV感染细胞系。我们还发现，与靶向位于gp 41 MPER中的近膜表位的抗体相比，靶向膜远端表位（包括V1/V2，V3和CD 4 b）的抗gp 160抗体更有可能激活针对gp 160+靶细胞的通用CAR-NK细胞。最后，我们证实，HIV感染的原代人CD 4 + T细胞可以有效地杀死使用相同的方法。鉴于具有不同抗原特异性的多种抗gp 160抗体很容易获得，这种模块化通用CAR-NK细胞平台可能会克服HIV多样性，从而提供一种有希望的根除HIV感染细胞的策略。
Engineering T cells and natural killer (NK) cells with anti-HIV chimeric antigen receptors (CAR) has emerged as a promising strategy to eradicate HIV-infected cells. However, current anti-HIV CARs are limited by targeting a single epitope of the HIV envelope glycoprotein gp160, which cannot counter the enormous diversity and mutability of viruses. Here, we report the development of a universal CAR-NK cell, which recognizes 2,4-dinitrophenyl (DNP) and can subsequently be redirected to target various epitopes of gp160 using DNP-conjugated antibodies as adaptor molecules. We show that this CAR-NK cell can recognize and kill mimic HIV-infected cell lines expressing subtypes B and C gp160. We additionally find that anti-gp160 antibodies targeting membrane-distal epitopes (including V1/V2, V3, and CD4bs) are more likely to activate universal CAR-NK cells against gp160+ target cells, compared with those targeting membrane-proximal epitopes located in the gp41 MPER. Finally, we confirm that HIV-infected primary human CD4+ T cells can be effectively killed using the same approach. Given that numerous anti-gp160 antibodies with different antigen specificities are readily available, this modular universal CAR-NK cell platform can potentially overcome HIV diversity, thus providing a promising strategy to eradicate HIV-infected cells.
登录
查看更多内容
影响因子：
32.4
作者：
Adams JJ;Narayanan S;Liu B;Birnbaum ME;Kruse AC;Bowerman NA;Chen W;Levin AM;Connolly JM;Zhu C;Kranz DM;Garcia KC
通讯作者：
Garcia KC
影响因子：
64.5
作者：
Bournazos S;Gazumyan A;Seaman MS;Nussenzweig MC;Ravetch JV
通讯作者：
Ravetch JV
DOI：
10.1073/pnas.1807259115
发表时间：
2018-09-18
影响因子：
11.1
作者：
Fu, Qingshan;Shaik, Md Munan;Chou, James J.
通讯作者：
Chou, James J.
影响因子：
64.8
作者：
Deng, Kai;Pertea, Mihaela;Rongvaux, Anthony;Wang, Leyao;Durand, Christine M.;Ghiaur, Gabriel;Lai, Jun;McHugh, Holly L.;Hao, Haiping;Zhang, Hao;Margolick, Joseph B.;Gurer, Cagan;Murphy, Andrew J.;Valenzuela, David M.;Yancopoulos, George D.;Deeks, Steven G.;Strowig, Till;Kumar, Priti;Siliciano, Janet D.;Salzberg, Steven L.;Flavell, Richard A.;Shan, Liang;Siliciano, Robert F.
通讯作者：
Siliciano, Robert F.
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL