Nakajima Oumi, Ichimaru Daiju, Urata Yasuo, Fujiwara Toshiyoshi, Horibe Tomohisa, Kohno Masayuki, Kawakami Koji
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto 606-8501, Japan.
Oncol Rep. 2009 Nov;22(5):1039-43. doi: 10.3892/or_00000533.
We previously reported that telomerase-specific replication-component adenovirous, Telomelysin (OBP-301) has cytotoxic activity to the YCUT892, KCCT873, KCCT891, KCCL871, YCUM862, HN12, and KCCOR891 cell lines in vitro, and investigated the association between cytotoxic activity and adenoviral receptor expression. In this study, we evaluated the most appropriate way to administer telomelysin (OBP-301) in the treatment of squamous cell carcinoma of the head and neck (SCCHN), and assessed the effect of OBP-301 in large subcutaneous KCCT873 human SCCHN tumors in immunodeficient mice. We also compared antitumor responses following three intratumoral (i.t.) injections of OBP-301 given daily, every 2 days or weekly. To investigate the mechanism of the antitumor effect, we evaluated cellular infiltration in treated tumors. OBP-301 showed remarkable antitumor activity against large KCCT873 tumors, and three treatment schedules produced similar antitumor effects. The weekly regimen also significantly reduced the growth of large tumors. Immunochemistry revealed that macrophages, but not natural killer cells, were responsible for tumor regression. A regimen of three weekly injections of OBP-301 has remarkable antitumor effects against large KCCT873 tumors. These results may provide a new platform for treating patients with localized SCCHN.
我们之前报道过,端粒酶特异性复制组件腺病毒Telomelysin(OBP - 301)在体外对YCUT892、KCCT873、KCCT891、KCCL871、YCUM862、HN12和KCCOR891细胞系具有细胞毒性活性,并研究了细胞毒性活性与腺病毒受体表达之间的关联。在本研究中,我们评估了在头颈部鳞状细胞癌(SCCHN)治疗中给予Telomelysin(OBP - 301)的最合适方式,并评估了OBP - 301对免疫缺陷小鼠体内大型皮下KCCT873人SCCHN肿瘤的作用。我们还比较了每日、每2天或每周进行三次瘤内(i.t.)注射OBP - 301后的抗肿瘤反应。为了研究抗肿瘤作用的机制,我们评估了治疗后肿瘤中的细胞浸润情况。OBP - 301对大型KCCT873肿瘤显示出显著的抗肿瘤活性,三种治疗方案产生了相似的抗肿瘤效果。每周给药方案也显著降低了大型肿瘤的生长。免疫化学分析显示,是巨噬细胞而非自然杀伤细胞导致了肿瘤消退。每周三次注射OBP - 301的方案对大型KCCT873肿瘤具有显著的抗肿瘤作用。这些结果可能为治疗局限性SCCHN患者提供一个新的平台。