Establishment of biological and pharmacokinetic assays of telomerase-specific replication-selective adenovirus

摘要: The use of replication-selective tumor-specific viruses represents a novel approach for the treatment neoplastic disease. We constructed an attenuated adenovirus, telomerase-specific adenovirus (TRAD), in which human telomerase reverse transcriptase promoter element drives expression E1A and E1B genes linked with internal ribosome entry site (IRES). Forty-eight hours after TRAD infection at multiplicity 1.0, cell viability H1299 lung cancer cells was consistently less than 50% therefore this procedure could be used as potency assay to assess biological activity TRAD. also established quantitative real-time polymerase chain reaction (PCR) analysis consensus primers either or IRES sequence. linear ranges quantitation were 10(3)-10(8) 10(2)-10(8) plaque-forming units/mL plasma, respectively. PCR demonstrated that levels normal tissues more 10(3) lower tumors A549 tumor xenografts nu/nmicro mice 28 days intratumoral injection. Our results suggest cell-killing against can biodistribution clinical trials.