title: Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain.
abstract: To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the gamma subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: P
authors.initials: P
authors.lastname: Hwu
authors.forename: G E
authors.initials: GE
authors.lastname: Shafer
authors.forename: J
authors.initials: J
authors.lastname: Treisman
authors.forename: D G
authors.initials: DG
authors.lastname: Schindler
authors.forename: G
authors.initials: G
authors.lastname: Gross
authors.forename: R
authors.initials: R
authors.lastname: Cowherd
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Z
authors.initials: Z
authors.lastname: Eshhar
mesh_terms: D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D017452:Receptors, IgG / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014162:Transfection
chemical_list: D007135:Immunoglobulin Variable Region; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor