学術雑誌論文 Utility of epirubicin-incorporating micelles tagged with anti-tissue factor antibody clone with no anticoagulant effect

Sugaya, Akinori  ,  Hyodo, Ichinosuke  ,  Koga, Yoshikatsu  ,  Yamamoto, Yoshiyuki  ,  Takashima, Hiroki  ,  Sato, Ryuta  ,  Tsumura, Ryo  ,  Furuya, Fumiaki  ,  Yasunaga, Masahiro  ,  Harada, Mitsunori  ,  Tanaka, Ryosuke  ,  Matsumura, Yasuhiro

107 ( 3 )  , pp.335 - 340 , 2016-03 , Wiley
ISSN:1347-9032
NII書誌ID(NCID):AA11808050
内容記述
Tissue factor (TF), an initiator of the extrinsic blood coagulation cascade, is overexpressed in different types of cancer. Tissue factor overexpression is also known as a poor prognostic factor in pancreatic cancer. We recently developed anti-TF antibody (clone1849)-conjugated epirubicin-incorporating micelles (NC-6300), and reported that this anti-TF1849-NC-6300 showed enhanced antitumor activity against TF-high expressed human pancreatic cancer cells, when compared with NC-6300 alone. However, clone 1849 antibody inhibited TF-associated blood coagulation activity. We studied another anti-TF antibody, clone 1859, which had no effect on blood coagulation and prepared anti-TF1859-NC-6300. In addition, to determine the optimum size of the antibody fragment to conjugate with NC-6300, three forms of the 1859 antibody (whole IgG, F[ab’]2, and Fab’) were conjugated to NC-6300. The antitumor effect of each anti-TF1859-NC-6300 was studied in vitro and in vivo, using two human pancreatic cancer cell lines, BxPC3 with high-expressed TF, and SUIT2 with low levels of TF. In vitro, all forms of anti-TF1859-NC-6300 showed higher cytocidal effects than NC-6300 in BxPC3, whereas this enhanced effect was not observed in SUIT2. Likewise, all forms of anti-TF1859-NC-6300 significantly suppressed tumor growth when compared to NC-6300 in the BxPC3, but not in the SUIT2, xenograft model. Among the three forms of conjugates, anti-TF1859-IgG-NC-6300 had a higher antitumor tendency in TF-high expressed cells. Thus, we have confirmed an enhanced antitumor effect of anti-TF1859-NC-6300 in a TF-high expressing tumor; anti-TF1859-IgG-NC-6300 could be used to simplify the manufacturing process of the antibody–micelle conjugation for future clinical studies.
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