Targeting of T lymphocytes to Neu/HER2-expressing cells using chimeric single chain Fv receptors.
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.
Stancovski
I
I
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Schindler
D G
DG
Waks
T
T
Yarden
Y
Y
Sela
M
M
Eshhar
Z
Z
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
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