Development of in vivo imaging and therapy for lymph node micrometastasis of cancer with telomerase-specific nano-bio oncolytic adenovirus

Replication-selective tumor-specific viruses present a novel and new approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. We further modified the E3 region of Telomelysin to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into HT29 tumors orthotopically implanted into the rectum of nude mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that TelomeScan causes viral spread into the regional lymphatic area and selectively replicates in cancer cells, resulting in GFP expression in metastatic lymph nodes. This technology is adaptable to detect lymph node micrometastasis. And our results also show that intratumoral injection of telomerase-specific oncolytic adenoviruses has a possible therapeutic effect at the primary site as well as metastatic lymph nodes in an orthotopic human rectal cancer xenograft model. The outcome has important implications for the treatment of lymph node metastasis of cancer. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.