Use of telomelysin (OBP-301) in mouse xenografts of human head and neck cancer.
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.
Nakajima
Oumi
O
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto 606-8501, Japan.
Ichimaru
Daiju
D
Urata
Yasuo
Y
Fujiwara
Toshiyoshi
T
Horibe
Tomohisa
T
Kohno
Masayuki
M
Kawakami
Koji
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D019098:Telomerase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D019098:Telomerase