Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool

  • Authors:
    • Ryo Tsumura
    • Ryuta Sato
    • Fumiaki Furuya
    • Yoshikatsu Koga
    • Yoshiyuki Yamamoto
    • Yuki Fujiwara
    • Masahiro Yasunaga
    • Yasuhiro Matsumura
  • View Affiliations

  • Published online on: October 19, 2015     https://doi.org/10.3892/ijo.2015.3210
  • Pages: 2107-2114
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Abstract

Tissue factor (TF) is expressed strongly in various types of cancer, especially cancers that are often refractory to treatment, such as pancreatic cancer. In this study, we compared the differences in the biophysical and pharmacological properties of whole IgG and the Fab fragment of anti-human TF monoclonal antibody (1849 antibodies), in order to determine their suitability for application in the diagnosis and treatment of cancers. In the biophysical examination, we investigated the characteristics of 1849-whole IgG and 1849-Fab by SPR sensing and confocal fluorescence microscopy analysis using recombinant human TF antigen and TF-overexpressing human pancreatic cancer cell line, BxPC3, respectively. After conjugation with Alexa-Flour-647, in vivo imaging was conducted in mice bearing BxPC3 xenograft tumors. Furthermore, the distribution of the conjugates in tumors and major organs was evaluated by ex vivo study. The in vitro experiments showed that 1849 antibodies had high affinity against TF antigen. In addition, 1849-Fab showed a faster dissociation rate from the antigen than 1849-whole IgG. In mice, 1849-Fab-Alexa-Flour-647 showed rapid renal clearance and faster tumor accumulation, achieving a high contrast signal over nearby normal tissues in the early phase and enhanced tumor penetration after administration. On the other hand, 1849-whole IgG-Alexa-Flour-647 showed slow clearance from the blood and sustained high tumor accumulation. These results suggest that 1849-Fab may be a useful tool for pancreatic cancer diagnosis.
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December-2015
Volume 47 Issue 6

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

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Spandidos Publications style
Tsumura R, Sato R, Furuya F, Koga Y, Yamamoto Y, Fujiwara Y, Yasunaga M and Matsumura Y: Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool. Int J Oncol 47: 2107-2114, 2015
APA
Tsumura, R., Sato, R., Furuya, F., Koga, Y., Yamamoto, Y., Fujiwara, Y. ... Matsumura, Y. (2015). Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool. International Journal of Oncology, 47, 2107-2114. https://doi.org/10.3892/ijo.2015.3210
MLA
Tsumura, R., Sato, R., Furuya, F., Koga, Y., Yamamoto, Y., Fujiwara, Y., Yasunaga, M., Matsumura, Y."Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool". International Journal of Oncology 47.6 (2015): 2107-2114.
Chicago
Tsumura, R., Sato, R., Furuya, F., Koga, Y., Yamamoto, Y., Fujiwara, Y., Yasunaga, M., Matsumura, Y."Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool". International Journal of Oncology 47, no. 6 (2015): 2107-2114. https://doi.org/10.3892/ijo.2015.3210