Anti-tumor effects of telomelysin for head and neck squamous cell carcinoma.
Telomelysin is a telomerase-specific replication-competent adenovirus with telomerase reverse transcriptase (hTERT) promoter, which has shown strong anti-tumor effects on a variety of human cancer cells. Human head and neck squamous cell carcinoma (HNSCC) cell lines and a murine HNSCC (NR-S1) model were used to investigate whether telomelysin (OBP-301) had a therapeutic efficacy for HNSCC. We examined the cell killing effects of telomelysin and the induction of tumor cell apoptosis by telomelysin in vitro. Based on these data, we examined whether telomelysin therapy produced therapeutic benefits in vivo. The results demonstrated that the treatment of telomelysin led to significant tumor regression on the side with subcutaneous NR-S1 tumor. We first confirmed the direct anti-tumor effect of intratumoral telomelysin injections in a murine HNSCC model. Further analyses of the augmented anti-tumor effects revealed that telomelysin increased the source of tumor antigens for immune cells, resulting in the induction of CD4+ and CD8+ T cells responsible for the in vivo tumor regression of treated and untreated tumors. Subsequently, an elevated IFN-gamma production of spleen cells was observed in mice treated with telomelysin. These results raise the possibility that telomelysin enhances the immune response in addition to its direct tumor cell killing activity. These findings suggest that telomelysin is a potent agent for the treatment of HNSCC patients with multiple metastases.
Fujita
Kyoko
K
Department of Biology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. t056043b@yokohama-cu.ac.jp
Kimura
Machiko
M
Kondo
Norio
N
Sakakibara
Atsuko
A
Sano
Daisuke
D
Ishiguro
Yukari
Y
Tsukuda
Mamoru
M
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents