Targeting the HIV reservoir:chimeric antigen receptor therapy for HIV cure  

作　　者：Shuang Li Hu Wang Na Guo Bin Su Olivier Lambotte Tong Zhang 

机构地区：[1]Beijing Key Laboratory for HIV/AIDS Research,Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection,Clinical and Research Center for Infectious Diseases,Beijing Youan Hospital,Capital Medical University,Beijing 100069,China [2]Department of Internal Medicine,AP-HP,Bicêtre Hospital,UMR1184 INSERM CEA,Le Kremlin Bicêtre,University Paris Saclay,Paris 94270,France

出　　处：《Chinese Medical Journal》2023年第22期2658-2667,共10页中华医学杂志（英文版）

基　　金：supported by grants from the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905);the National Natural Science Foundation of China(Nos.NSFC,81974303 and 82072271);Beijing Natural Science Foundation(Nos.L222068 and Z220018);the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(Nos.2022-2-018 and 2022-1-007);the Climbing the peak(Dengfeng)Talent Training Program of Beijing Hospitals Authority(Nos.DFL20191701);the Beijing Health Technologies Promotion Program(BHTPP202002)and Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089).

摘　　要：Although antiretroviral therapy(ART)can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus(HIV)-infected individuals,ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs.To achieve a functional cure for HIV infection,numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART.Early studies have tested adoptive T-cell therapies in HIV-infected individuals,but their effectiveness was limited.In recent years,with the technological progress and great success of chimeric antigen receptor(CAR)therapy in the treatment of hematological malignancies,CAR therapy has gradually shown its advantages in the field of HIV infection.Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells.Therefore,CAR therapy may be beneficial for enhancing HIV immunity,achieving HIV control,and eliminating HIV reservoirs,gradually becoming a promising strategy for achieving a functional HIV cure.In this review,we provide an overview of the design of anti-HIV CAR proteins,the cell types of anti-HIV CAR(including CAR T cells,CAR natural killer cells,and CAR-encoding hematopoietic stem/progenitor cells),the clinical application of CAR therapy in HIV infection,and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

关 键 词：Functional HIV cure HIV reservoir Chimeric antigen receptor therapy CAR T cells CAR natural killer cells 

分 类 号：R512.91[医药卫生—内科学]