Open AccessUtility of epirubicin‐incorporating micelles tagged with anti‐tissue factor antibody clone with no anticoagulant effect
Author(s) -
Sugaya Akinori,
Hyodo Ichinosuke,
Koga Yoshikatsu,
Yamamoto Yoshiyuki,
Takashima Hiroki,
Sato Ryuta,
Tsumura Ryo,
Furuya Fumiaki,
Yasunaga Masahiro,
Harada Mitsunori,
Tanaka Ryosuke,
Matsumura Yasuhiro
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12863
Subject(s) - tissue factor , antibody , clone (java method) , in vitro , microbiology and biotechnology , chemistry , pancreatic cancer , in vivo , cell culture , epirubicin , cancer research , cancer , coagulation , biology , immunology , medicine , biochemistry , dna , breast cancer , genetics
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‐ TF 1849‐ 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‐ TF 1859‐ 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‐ TF 1859‐ NC ‐6300 was studied in vitro and in vivo , using two human pancreatic cancer cell lines, Bx PC 3 with high‐expressed TF , and SUIT 2 with low levels of TF . In vitro , all forms of anti‐ TF 1859‐ NC ‐6300 showed higher cytocidal effects than NC ‐6300 in Bx PC 3, whereas this enhanced effect was not observed in SUIT 2. Likewise, all forms of anti‐ TF 1859‐ NC ‐6300 significantly suppressed tumor growth when compared to NC ‐6300 in the Bx PC 3, but not in the SUIT 2, xenograft model. Among the three forms of conjugates, anti‐ TF 1859‐IgG‐ NC ‐6300 had a higher antitumor tendency in TF ‐high expressed cells. Thus, we have confirmed an enhanced antitumor effect of anti‐ TF 1859‐ NC ‐6300 in a TF ‐high expressing tumor; anti‐ TF 1859‐IgG‐ NC ‐6300 could be used to simplify the manufacturing process of the antibody–micelle conjugation for future clinical studies.