Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils

  • Authors: Y. Tamamori, T. Sawada, T. Nishihara, Y. Yamashita, M. Ohira, J. J.L. Ho, Y.-S. Kim, K. Hirakawa-Ys Chung
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  • Published online on: Sunday, September 1, 2002
  • Pages: 649-654
  • DOI: 10.3892/ijo.21.3.649

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 Fcγ 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.
Journal Cover

September 2002
Volume 21 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Tamamori, Y., Sawada, T., Nishihara, T., Yamashita, Y., Ohira, M., Ho, J., Kim, Y., & Hirakawa-Ys Chung, K. (2002). Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils. International Journal of Oncology, 21(3), 649-654.
MLA
Tamamori, Sawada, Nishihara, Yamashita, Ohira, Ho, Kim, and K. Hirakawa-Ys Chung. "Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils." International Journal of Oncology International Journal of Oncology 21.3 (2002): 649-654.
Chicago
Tamamori, Sawada, Nishihara, Yamashita, Ohira, Ho, Kim, and K. Hirakawa-Ys Chung. "Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils." International Journal of Oncology International Journal of Oncology 21 no. 3 (2002): 649-654.