New approaches for the enhancement of chimeric antigen receptors for the treatment of HIV

  • Mayra A. Carrillo
    Division of Hematology & Oncology, Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, Calif
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  • Anjie Zhen
    Division of Hematology & Oncology, Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, Calif
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  • Jerome A. Zack
    Division of Hematology & Oncology, Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, Calif

    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Calif
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  • Scott G. Kitchen
    Reprint requests: Scott G. Kitchen, Division of Hematology & Oncology, Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, CA 90095
    Division of Hematology & Oncology, Department of Medicine, UCLA AIDS Institute, David Geffen School of Medicine University of California, Los Angeles, Calif
    Search for articles by this author
      HIV infection continues to be a life-long chronic disease in spite of the success of antiretroviral therapy (ART) in controlling viral replication and preventing disease progression. However, because of the high cost of treatment, severe side effects, and inefficiency in curing the disease with ART, there is a call for alternative therapies that will provide a functional cure for HIV. Cytotoxic T lymphocytes (CTLs) are vital in the control and clearance of viral infections and therefore immune-based therapies have attempted to engineer HIV-specific CTLs that would be able to clear the infection from the body. The development of chimeric antigen receptors (CARs) provides an opportunity to engineer superior HIV-specific CTLs that will be independent of the major histocompatibility complex for target recognition. A CD4-based CAR has been previously tested in clinical trials to test the antiviral efficacy of peripheral T cells armed with this CD4-based CAR. The results from these clinical trials showed the safety and feasibility of CAR T cell therapy for HIV infection; however, minimal antiviral efficacy was seen. In this review, we will discuss the various strategies being developed to enhance the therapeutic potency of anti-HIV CARs with the goal of generating superior antiviral responses that will lead to life-long HIV immunity and clearance of the virus from the body.


      bNAbs (broadly neutralizing antibodies), CAR (chimeric antigen receptor), CTL (cytotoxic T lymphocyte), HSC (hematopoietic stem cell), TCR (T cell receptor)
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