期刊论文详细信息
Cancer Science
Enhanced antitumor effect of anti‐tissue factor antibody‐conjugated epirubicin‐incorporating micelles in xenograft models
Yoshiyuki Yamamoto1  Ichinosuke Hyodo2  Yoshikatsu Koga1  Ryo Tsumura1  Ryuta Sato1  Toshihumi Obonai1  Hirobumi Fuchigami1  Fumiaki Furuya1  Masahiro Yasunaga1  Mitsunori Harada3  Yasuki Kato3  Atsushi Ohtsu4 
[1] Division of Developmental Therapeutics, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan;Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan;Research Division, NanoCarrier Co. Ltd., Kashiwa, Japan;Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan
关键词: Antibody drug conjugate;    drug delivery system;    epirubicin;    polymeric micelles;    tissue factor;   
DOI  :  10.1111/cas.12645
来源: Wiley
PDF
【 摘 要 】

Abstract

For the creation of a successful antibody–drug conjugate (ADC), both scientific and clinical evidence has indicated that highly toxic anticancer agents (ACA) should be conjugated to a monoclonal antibody (mAb) to administer a reasonable amount of ADC to patients without compromising the affinity of the mAb. For ordinary ACA, the conjugation of a mAb to ACA-loaded micellar nanoparticles is clinically applicable. Tissue factor (TF) is often overexpressed in various cancer cells and tumor vascular endothelium. Accordingly, anti-TF-NC-6300, consisting of epirubicin-incorporating micelles (NC-6300) conjugated with the F(ab')2 of anti-TF mAb was developed. The in vitro and in vivo efficacy and pharmacokinetics of anti-TF-NC-6300 were compared to NC-6300 using two human pancreatic cancer cell lines, BxPC3 (high TF expression) and SUIT2 (low TF expression), and a gastric cancer cell line, 44As3 (high TF expression). The intracellular uptake of epirubicin was faster and greater in BxPC3 cells treated with anti-TF-NC-6300, compared with NC-6300. Anti-TF-NC-6300 showed a superior antitumor activity in BxPC3 and 44As3 xenografts, compared with NC-6300, while the activities of both micelles were similar in the SUIT2 xenograft. A higher tumor accumulation of anti-TF-NC-6300 compared to NC-6300 was seen, regardless of the TF expression levels. However, anti-TF-NC-6300 appeared to be localized to the tumor cells with high TF expression. These results indicated that the enhanced antitumor effect of anti-TF-NC6300 may be independent of the tumor accumulation but may depend on the selective intratumor localization and the preferential internalization of anti-TF-NC-6300 into high TF tumor cells.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

【 预 览 】
附件列表
Files Size Format View
RO202107150002512ZK.pdf 2711KB PDF download
  文献评价指标  
  下载次数:3次 浏览次数:1次