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

Chinese Medical Journal 2023年第22期136卷 2658-2667页

作者： Shuang Li Hu Wang Na Guo Bin Su Olivier Lambotte Tong Zhang Beijing Key Laboratory for hiv/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Department of Internal Medicine AP-HPBicêtre HospitalUMR1184 INSERM CEALe Kremlin BicêtreUniversity Paris SaclayParis 94270France

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 *** 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 *** studies have tested adoptive T-cell therapies in hiv-infected individuals,but their effectiveness was *** 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 *** studies have identified a variety of hiv-specific CAR structures and types of cytolytic effector ***,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 *** 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

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hiv reservoir: antiviral immune responses and immune interventions for curing hiv infection

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Chinese Medical Journal 2022年第22期135卷 2667-2676页

作者： Shuang Li Christiane Moog Tong Zhang Bin Su Beijing Key Laboratory for hiv/AIDS Research Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV InfectionClinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China Laboratoire d’ImmunoRhumatologie Moléculaire Institut national de la santéet de la recherche médicale(INSERM)UMR_S 1109Institut thématique interdisciplinaire(ITI)de Médecine de Précision de StrasbourgTransplantex NGFacultéde MédecineFédération Hospitalo-Universitaire OMICAREFédération de Médecine Translationnelle de Strasbourg(FMTS)Universitéde StrasbourgStrasbourg 67000France

Antiretroviral therapy against human immunodeficiency virus (hiv) is effective in controlling viral replication but cannot completely eliminate hiv due to the persistence of the hiv reservoir. Innate and adaptive immune responses have been proposed to contribute to preventing hiv acquisition, controlling hiv replication and eliminating hiv-infected cells. However, the immune responses naturally induced in hiv-infected individuals rarely eradicate hiv infection, which may be caused by immune escape, an inadequate magnitude and breadth of immune responses, and immune exhaustion. Optimizing these immune responses may solve the problems of epitope escape and insufficient sustained memory responses. Moreover, immune interventions aimed at improving host immune response can reduce hiv reservoirs, which have become one focus in the development of innovative strategies to eliminate hiv reservoirs. In this review, we focus on the immune response against hiv and how antiviral immune responses affect hiv reservoirs. We also discuss the development of innovative strategies aiming to eliminate hiv reservoirs and promoting functional cure of hiv infection.

关键词： Antiviral immune response functional hiv cure hiv reservoir Human immunodeficiency virus Immune interventions

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