title: Targeting of human immunodeficiency virus-infected cells by CD8+ T lymphocytes armed with universal T-cell receptors.
abstract: We have developed an immunotherapeutic approach with potential application in the treatment of viral and malignant disease. We show that primary CD8+ T cells isolated from peripheral blood can be genetically modified by retroviral transduction to express high levels of universal (major histocompatibility complex-unrestricted) chimeric T-cell receptors specific for human immunodeficiency virus (HIV) antigens. Two classes of HIV-specific URs in which the antigen-binding domain is comprised of either CD4 or a single-chain antibody are capable of activating a number of T-cell effector functions in response to target cells, including cytolysis, in a highly sensitive and specific manner. Importantly, we have addressed a number of issues which, although particularly relevant to the clinical application of this approach in the treatment of HIV infection, may also impact on the potential of UR immunotherapy for other disease targets. The UR immunotherapeutic system is particularly suited for evaluation in the clinical setting.
authors.affiliation: Cell Genesys Inc, Foster City, CA.
authors.forename: M R
authors.initials: MR
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: A C
authors.initials: AC
authors.lastname: Tran
authors.forename: T J
authors.initials: TJ
authors.lastname: Dull
authors.forename: J E
authors.initials: JE
authors.lastname: Groopman
authors.forename: D J
authors.initials: DJ
authors.lastname: Capon
authors.forename: R A
authors.initials: RA
authors.lastname: Byrn
authors.forename: M H
authors.initials: MH
authors.lastname: Finer
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000628:therapy*; D007111:Immunity, Cellular; D007167:Immunotherapy; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins