Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils
| Autor: | Yutaka Tamamori, Yoshito Yamashita, Tamahiro Nishihara, Tetsuji Sawada, Jenny J. L. Ho, Young-Sik Kim, Masaichi Ohira, Kosei Hirakawa-Y.S. Chung |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
medicine.drug_class Neutrophils Mice Nude chemical and pharmacologic phenomena Receptors Fc CD16 Biology Granulocyte Monoclonal antibody Peripheral blood mononuclear cell Mice Nude mouse Granulocyte Colony-Stimulating Factor medicine Tumor Cells Cultured Animals Humans Cytotoxicity Antibody-dependent cell-mediated cytotoxicity Mice Inbred BALB C Receptors IgG Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal hemic and immune systems Drug Synergism biology.organism_classification Xenograft Model Antitumor Assays Pancreatic Neoplasms medicine.anatomical_structure Oncology Immunology Cancer research biology.protein Immunotherapy Antibody |
| Zdroj: | International journal of oncology. 21(3) |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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