title: Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors.
abstract: Cell surface molecules essential for the transformed phenotype or growth of malignant cells are attractive targets for anticancer immunotherapy. Antibodies specific to Neu/HER2, a human adenocarcinoma-associated growth factor receptor, were demonstrated to have tumor-inhibitory capacity. Yet, the inefficient accessibility of antibodies to solid tumors limits their clinical use. To redirect effector lymphocytes to adenocarcinomas, we constructed and functionally expressed in T cells chimeric single chain receptor genes incorporating both the Ag-binding domain of anti-Neu/HER2 antibodies and the zeta-signal-transducing subunit of the TCR/CD3 complex or the gamma-signal-transducing subunit of the Ig Fc receptor complex. Surface expression of the anti-Neu/HER2 chimeric genes in cytotoxic T cell hybridomas endowed them with specific Neu/HER2 recognition enabling their activation for IL-2 production and lysis of transformed cells overexpressing Neu/HER2. These chimeric genes hold promise for the immunotherapy of cancer.
authors.affiliation: Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Stancovski
authors.forename: D G
authors.initials: DG
authors.lastname: Schindler
authors.forename: T
authors.initials: T
authors.lastname: Waks
authors.forename: Y
authors.initials: Y
authors.lastname: Yarden
authors.forename: M
authors.initials: M
authors.lastname: Sela
authors.forename: Z
authors.initials: Z
authors.lastname: Eshhar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D066246:ErbB Receptors / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011961:Receptors, Fc / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D066246:ErbB Receptors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C054979:antigen T cell receptor, zeta chain