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
  • View Affiliations

  • Published online on: September 1, 2002     https://doi.org/10.3892/ijo.21.3.649
  • Pages: 649-654
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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.

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September 2002
Volume 21 Issue 3

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

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Spandidos Publications style
Tamamori Y, Sawada T, Nishihara T, Yamashita Y, Ohira M, Ho JJ, Kim Y and Hirakawa-Ys Chung K: Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils. Int J Oncol 21: 649-654, 2002
APA
Tamamori, Y., Sawada, T., Nishihara, T., Yamashita, Y., Ohira, M., Ho, J.J. ... 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, 649-654. https://doi.org/10.3892/ijo.21.3.649
MLA
Tamamori, Y., Sawada, T., Nishihara, T., Yamashita, Y., Ohira, M., Ho, J. J., Kim, Y., Hirakawa-Ys Chung, K."Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils". International Journal of Oncology 21.3 (2002): 649-654.
Chicago
Tamamori, Y., Sawada, T., Nishihara, T., Yamashita, Y., Ohira, M., Ho, J. J., Kim, Y., Hirakawa-Ys Chung, K."Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils". International Journal of Oncology 21, no. 3 (2002): 649-654. https://doi.org/10.3892/ijo.21.3.649