title: Antitumor effects of cisplatin combined with tecemotide immunotherapy in a human MUC1 transgenic lung cancer mouse model.
abstract: The goals of the present study were to define the effects of simultaneous cisplatin/tecemotide therapy on tumor development in a human mucin 1 (MUC1) transgenic lung cancer mouse model and to examine the effects of radiotherapy (RTX) on splenocytes, serum cytokines, and immune response to tecemotide. Two hundred twenty-six human MUC1 transgenic C57BL/6 mice were used in five studies designed to assess (i) serum cytokine and immune responses following four weekly 10-μg doses of tecemotide; (ii) the effects of simultaneous administration of cisplatin (2.5 mg/kg × 2 doses/cycle × 4 cycles) and tecemotide (2 cycles × 8 weekly 10-μg doses/cycle) therapy on tumor development, serum cytokines, and immune response; (iii) the dose-response effects of RTX on lymphocyte counts 16 hours following doses of 2 to 8 Gy; (iv) the time course of lymphocyte recovery from 16 hours to 20 days following 8-Gy RTX; and (v) the effects of simultaneous administration of RTX (8 Gy) and tecemotide on the immune response to tecemotide (four weekly 10-μg doses). Serum cytokines were analyzed by multiplex immunoassay, IFNγ immune responses by enzyme-linked immunosorbent spot (ELISpot), and lung tumor foci by lung whole mounts. Simultaneous cisplatin/tecemotide therapy resulted in significant and additive reduction in lung tumor foci compared with control mice, with significantly elevated serum IFNγ levels and specific IFNγ immune responses observed in both tecemotide and tecemotide + cisplatin-treated mice. Finally, neither cisplatin nor radiation interfered with the immune response to tecemotide.
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Chiao-Jung
authors.initials: CJ
authors.lastname: Kao
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wurz
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Arta M
authors.initials: AM
authors.lastname: Monjazeb
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Vang
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Cadman
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Griffey
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Authors' Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Department of Radiation Oncology, University of California, Davis, Sacramento; Comparative Pathology Laboratory, UC Davis School of Veterinary Medicine, University of California, Davis, Davis, California; and Department of ImmunoOncology, Merck Serono Research, Merck KGaA, Darmstadt, Germany mwdegregorio@ucdavis.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: DeGregorio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000528:radiation effects; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; C518273:L-BLP25; D008562:Membrane Glycoproteins; D018396:Mucin-1; D002945:Cisplatin