title: Pegfilgrastim Enhances the Antitumor Effect of Therapeutic Monoclonal Antibodies.
abstract: Therapeutic mAbs exert antitumor activity through various mechanisms, including apoptotic signalization, complement-dependent cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP). G-CSF and GM-CSF have been reported to increase the activity of antibodies in preclinical models and in clinical trials. To determine the potential role of pegfilgrastim as an enhancer of anticancer antibodies, we performed a comparative study of filgrastim and pegfilgrastim. We found that pegfilgrastim was significantly more potent than filgrastim in murine xenograft models treated with mAbs. This was observed with rituximab in CD20(+) models and with trastuzumab in HER2(+) models. Stimulation with pegfilgrastim was associated with significant enhancement of leukocyte content in spleen as well as mobilization of activated monocytes/granulocytes from the spleen to the tumor bed. These results suggest that pegfilgrastim could constitute a potent adjuvant for immunotherapy with mAbs possessing ADCC/ADCP properties. Mol Cancer Ther; 15(6); 1238-47. ©2016 AACR.
authors.affiliation: Hospices Civils de Lyon, Pierre Bénite, France. Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cornet
authors.affiliation: Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Mathé
authors.affiliation: Hospices Civils de Lyon, Pierre Bénite, France. Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Kamel
authors.initials: K
authors.lastname: Chettab
authors.affiliation: Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Evesque
authors.affiliation: Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: Eva-Laure
authors.initials: EL
authors.lastname: Matera
authors.affiliation: Département d'Oncologie Médicale, Centre de Lutte Contre le Cancer Lyon et Rhône-Alpes, Lyon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.affiliation: Hospices Civils de Lyon, Pierre Bénite, France. Université de Lyon, Lyon, France. INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. charles.dumontet@chu-lyon.fr.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D000069585:Filgrastim / Q000008:administration & dosage* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D000069283:Rituximab / Q000008:administration & dosage / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D000068878:Trastuzumab / Q000008:administration & dosage / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069283:Rituximab; D000068878:Trastuzumab; D000069585:Filgrastim