HIV-specific chimeric antigen receptor (CAR) T-cells have been developed to target HIV-1 infected CD4+ T-cells that express HIV Env proteins. However, T cell exhaustion and the patient-specific autologous paradigm of CAR-T cell hurdled clinical applications. Here, we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27 (3BE) CAR construct that enabled the expression of programmed cell death protein (PD-1) -blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV Env. Compared with T cells expressing 3BNC117-CAR alone, 3BE CAR-T cells showed greater cytotoxic activity against HIV Env+ cells with stronger proliferation capability, higher killing efficiency, and enhanced cytokine secretion in the presence of HIV Env-expressing cells. Furthermore, we manufactured TCR-deficient 3BE CAR-T cells through gene editing and demonstrated that these CAR-T cells could effectively kill HIV Env ​+ ​cells in vivo without the occurrence of severe graft-versus-host disease (GvHD) in NSG mice. These data suggest that we have provided a feasible approach to the generation of "off-the-shelf" anti-HIV CAR-T cells in combination with PD-1 checkpoint blockade immunotherapy, which can be a powerful therapeutic candidate for the functional cure of HIV.Keywords: Anti-HIV CAR-T; Cellular immunotherapy; PD-1 blocking; TCR disruption.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。