title: Engineering HIV-Specific Immunity with Chimeric Antigen Receptors.
abstract: HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections. There are considerable efforts to enhance CTL responses in HIV-infected individuals in hopes of providing the immune response with armaments to more effectively control viral replication. In this review, we discuss some of these efforts and focus on the development of a gene therapy-based approach to engineer hematopoietic stem cells with an HIV-1-specific chimeric antigen receptor, which seeks to provide an inexhaustible source of HIV-1-specific immune cells that are MHC unrestricted and superior to natural antiviral T cell responses. These efforts provide the basis for further development of T cell functional enhancement to target and treat chronic HIV infection in hopes of eradicating the virus from the body.
authors.affiliation: 1 Division of Hematology/Oncology, Department of Medicine, and UCLA Center for AIDS Research, UCLA AIDS Institute , David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Kitchen
authors.affiliation: 1 Division of Hematology/Oncology, Department of Medicine, and UCLA Center for AIDS Research, UCLA AIDS Institute , David Geffen School of Medicine at UCLA, Los Angeles, California.|2 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA , Los Angeles, California.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods; D006678:HIV / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D011946:Receptors, Antigen / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
chemical_list: D011946:Receptors, Antigen
keywords: CD8+ T cells; HIV immunity; chimeric antigen receptors; engineered immunity; immunotherapy