Yano Shuya, Takehara Kiyoto, Miwa Shinji, Kishimoto Hiroyuki, Tazawa Hiroshi, Urata Yasuo, Kagawa Shunsuke, Bouvet Michael, Fujiwara Toshiyoshi, Hoffman Robert M
AntiCancer, Inc., San Diego, CA, USA.
Department of Surgery, University of California San Diego, CA, USA.
Oncotarget. 2016 Nov 15;7(46):75635-75647. doi: 10.18632/oncotarget.12314.
We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.
我们之前研发了一种基因工程改造的、表达绿色荧光蛋白(GFP)的端粒酶依赖性腺病毒OBP-401,它能够选择性地照亮癌细胞。在本报告中,我们证明,用OBP-401靶向接种于裸鼠体内原位生长的三阴性高侵袭性人类乳腺癌,能够实现治愈性荧光引导手术(FGS)。由于该病毒具有选择性标记并随后杀死癌细胞的能力,OBP-401实现了完全切除,预防了局部复发,并极大地抑制了淋巴结转移。相比之下,残余的乳腺癌细胞在明(白)光手术(BLS)后会变得更具侵袭性。与传统的BLS相比,基于OBP-401的FGS还提高了总生存率。因此,在临床相关的小鼠模型中,FGS可以预防高侵袭性三阴性乳腺癌的转移。