title: Cytokine-mediated enhancement of epidermal growth factor receptor expression provides an immunological approach to the therapy of pancreatic cancer.
abstract: The increased expression of epidermal growth factor receptor induced by tumor necrosis factor alpha renders pancreatic cancer cells more susceptible to antibody-dependent cellular cytotoxicity by a mAb specific for this receptor. Laboratory studies with athymic mice bearing xenografts of human pancreatic cancer cells demonstrated a cytokine-induced ability of the mAb to cause significant tumor regression. In a phase I/II clinical trial, 26 patients with unresectable pancreatic cancer were enrolled into three cohorts receiving variable amounts of the antibody together with a constant amount of tumor necrosis factor alpha. With increasing doses of antibody, the growth of the primary tumor was significantly inhibited. This was reflected by a longer median survival, with one complete remission lasting for 3 years obtained with the highest dose of antibody employed. Thus, a combination of the cytokine, tumor necrosis factor alpha, with a mAb to the epidermal growth factor receptor offers a potentially useful approach for the treatment of pancreatic cancer.
authors.affiliation: Medizinische Universitätsklinik, Knappschaftskrankenhaus, Ruhr-Universität Bochum, 44892 Bochum, Germany. wolff.schmiegel@rz.ruhr-uni-bochum.de
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.forename: J
authors.initials: J
authors.lastname: Schmielau
authors.forename: D
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: H
authors.initials: H
authors.lastname: Juhl
authors.forename: C
authors.initials: C
authors.lastname: Roeder
authors.forename: P
authors.initials: P
authors.lastname: Buggisch
authors.forename: A
authors.initials: A
authors.lastname: Onur
authors.forename: B
authors.initials: B
authors.lastname: Kremer
authors.forename: H
authors.initials: H
authors.lastname: Kalthoff
authors.forename: E V
authors.initials: EV
authors.lastname: Jensen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D066246:ErbB Receptors