Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents
| Autor: | Larry Boyle, Leisa Johnson, Frank McCormick, Annie Shen, John Kunich, Ali Fattaey, Terry Hermiston, Marilyn Lemmon, Marty Giedlin, Kusum Pandey |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
DNA Replication
Gene Expression Regulation Viral Cancer Research Genetic Vectors Transplantation Heterologous Antineoplastic Agents Cell Cycle Proteins Biology Virus Replication Retinoblastoma Protein Defective virus Retinoblastoma-like protein 1 Mice Viral life cycle Tumor Cells Cultured medicine Animals Humans Promoter Regions Genetic E2F Mice Knockout Retinoblastoma Adenoviruses Human Cell Cycle DNA replication Defective Viruses Neoplasms Experimental Cell Biology Fibroblasts medicine.disease In vitro E2F Transcription Factors DNA-Binding Proteins Survival Rate Oncology DNA Viral Systemic administration Cancer research Adenovirus E1A Proteins Transcription Factors |
| Zdroj: | Cancer Cell. 1:325-337 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/s1535-6108(02)00060-0 |
| Popis: | We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastoma tumor suppressor protein (pRB) pathway. Early and late viral gene expression as well as DNA replication were significantly reduced in a functional pRB-pathway-dependent manner, resulting in a restricted replication profile similar to that of nonreplicating adenoviruses in normal cells both in vitro and in vivo. In contrast, the viral life cycle and tumor cell killing activity of ONYX-411 was comparable to that of wild-type adenovirus following infection of human tumor cells in vitro as well as after systemic administration in tumor-bearing animals. |
| Databáze: | OpenAIRE |
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