Amagai Yosuke, Fujiyuki Tomoko, Yoneda Misako, Shoji Koichiro, Furukawa Yoichi, Sato Hiroki, Kai Chieko
Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Division of Clinical Genome Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2016 Apr 19;6:24572. doi: 10.1038/srep24572.
Oncolytic virotherapy is a distinctive antitumor therapy based on the cancer-cell-specific infectivity and killing activity of viruses, which exert a considerable antitumor effect with only a few treatments. Because colorectal cancer cells often acquire resistance to the molecular-targeted therapies and alternative treatments are called for, in this study, we evaluated the oncolytic activity against colorectal cancer cells of a recombinant measles virus (rMV-SLAMblind), which is blind to signaling lymphocytic activation molecule (SLAM) and infects target cells via nectin-4/poliovirus receptor-related 4 protein. We examined 10 cell lines including 8 cell lines that were resistant to epidermal-growth-factor-receptor (EGFR) targeted therapy. rMV-SLAMblind infected and lysed the nectin-4-positive cell lines dependently on nectin-4 expression, in spite of mutation in EGFR cascade. Tumour progression in xenograft models was also abrogated by the virus, and the infection of cancer cells in vivo by the virus was demonstrated with both flow cytometry and a histological analysis. Therefore, rMV-SLAMblind is considered a novel therapeutic agent for colorectal cancers, including those resistant to molecular-targeted therapies.
溶瘤病毒疗法是一种独特的抗肿瘤疗法，基于病毒对癌细胞的特异性感染和杀伤活性，只需少数几次治疗就能产生显著的抗肿瘤效果。由于结肠直肠癌细胞常常对分子靶向疗法产生耐药性，因此需要替代治疗方法。在本研究中，我们评估了一种重组麻疹病毒（rMV-SLAMblind）对结肠直肠癌细胞的溶瘤活性，该病毒对信号淋巴细胞激活分子（SLAM）无反应，并通过nectin-4/脊髓灰质炎病毒受体相关4蛋白感染靶细胞。我们检测了10种细胞系，其中包括8种对表皮生长因子受体（EGFR）靶向治疗耐药的细胞系。尽管EGFR级联发生了突变，但rMV-SLAMblind仍能依赖nectin-4的表达感染并裂解nectin-4阳性细胞系。病毒还消除了异种移植模型中的肿瘤进展，并且通过流式细胞术和组织学分析证实了病毒在体内对癌细胞的感染。因此，rMV-SLAMblind被认为是一种针对结肠直肠癌的新型治疗药物，包括那些对分子靶向疗法耐药的癌症。
