title: Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils.
abstract: Nd2 is a monoclonal antibody against pancreatic cancer. We have previously reported that human/mouse chimeric antibody Nd2 (c-Nd2) can induce antibody-dependent cell-mediated cytotoxicity (ADCC) with peripheral blood mononuclear cells (PBMs) as effectors. In this study, we investigated whether c-Nd2 can induce ADCC with poly-morphonuclear neutrophils (PMNs) as effector cells and the effects of granulocyte-colony stimulating factor (G-CSF) in enhancing this cytotoxicity. Cytotoxicities for pancreatic cancer cell line, SW1990 were dose-dependently increased by c-Nd2 during co-culture with PMNs and these cytotoxicities were significantly suppressed by the addition of neutralizing antibodies against CD16, which is Fcgamma receptor expressed on PMN membranes. PMNs treated with G-CSF significantly enhanced in vitro ADCC activity against SW1990 induced by c-Nd2. The in vivo growth of subcutaneously transplanted SW1990 tumor in nude mouse was significantly inhibited by i.p. administration of c-Nd2 compared to control (non-specific IgG1). In addition, this inhibitory effect was enhanced by the combination of c-Nd2 and G-CSF. Immunohistochemical study with anti-mouse neutrophil elastase antibody demonstrated strong infiltrations of PMNs into and around the transplanted tumor, treated with c-Nd2 and G-CSF. These results suggest that PMNs play an important role in c-Nd2 inducing ADCC and that combination immunotherapy of c-Nd2 with G-CSF may have clinical applications in the treatment of patients with pancreatic cancer by enhancing ADCC.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tamamori
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Tamahiro
authors.initials: T
authors.lastname: Nishihara
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Masaichi
authors.initials: M
authors.lastname: Ohira
authors.forename: Jenny J L
authors.initials: JJ
authors.lastname: Ho
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa-Y S Chung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000628:therapy*; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D011961:Receptors, Fc; D017452:Receptors, IgG; D016179:Granulocyte Colony-Stimulating Factor