Antihuman epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab enhances cytolytic activity of class I-restricted HER2-specific T lymphocytes against HER2-overexpressing tumor cells.
The monoclonal antibody trastuzumab (Herceptin) directed against the human epidermal growth factor receptor 2 (HER2) results in tumor regressions when administered to patients with HER2-overexpressing breast cancer. One of the underlying mechanisms of this antibody-induced tumor regression is based on the internalization and degradation of HER2 by tumor cells on interaction with trastuzumab, subsequently inhibiting signal transduction pathways. As antibody-induced degradation of HER2 is likely to be accompanied with increased numbers of HER2 peptides presented with MHC, we asked whether trastuzumab-treated tumor cells were more susceptible to CTL-mediated lysis. Here we show that the cytolytic activity of human, HER2-specific CD8(+) CTLs is augmented by anti-HER2 antibody trastuzumab. HER2-reactive CTL clones lyse class I-matched, HER2-overexpressing tumor cells more efficiently after treatment with trastuzumab. The potentially synergistic activity of HER2-specific antibody and CTL encourages the development of an HER2-targeted immunotherapy using a combination of inhibitory antibodies and CTLs for patients with HER2-overexpressing tumors.
zum Büschenfelde
Christian Meyer
CM
Department of Hematology/Oncology, Klinikum rechts der Isar, Technical University of Munich, Ismaningerstrasse 22, D-81675 Munich, Germany.
Hermann
Christine
C
Schmidt
Burkhard
B
Peschel
Christian
C
Bernhard
Helga
H
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab