Novel immunocompetent murine tumor model for evaluation of conditionally replication-competent (oncolytic) murine adenoviral vectors.

Oncolytic adenoviral vectors that express immunostimulatory transgenes are currently being evaluated in clinic. Preclinical testing of these vectors has thus far been limited to immunodeficient xenograft tumor models since human adenoviruses do not replicate effectively in murine tumor cells. The effect of the immunostimulatory transgene on overall virus potency can therefore not be readily assessed in these models.

Development of transcriptionally regulated oncolytic adenoviruses.

Changes initiated at the cellular and systemic levels as a result of viral infection or neoplastic transformation share significant overlap. Therefore, the use of replicating viruses to treat tumors has long been postulated as a promising avenue for oncolytic therapy. Over the last 10 years, transcriptionally regulated adenoviruses have become a popular platform for the development of such oncolytic viruses.

Oncolytic adenovirus CG7870 in combination with radiation demonstrates synergistic enhancements of antitumor efficacy without loss of specificity.

Conditionally replicating adenoviruses that selectively replicate in tumor cells, but not in normal cells, are being explored as virotherapeutic agents for cancer. A prostate-specific oncolytic adenovirus, CG7870 is currently being evaluated in phase 1/2 clinical trials for the treatment of prostate cancer. To decrease the effective dose and further increase the therapeutic efficacy of CG7870, the combination of virotherapy with radiation therapy was explored in this study.

Carcinoembryonic antigen-producing cell-specific oncolytic adenovirus, OV798, for colorectal cancer therapy.

Human carcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers and has been widely used as a clinical marker for the management of colon cancer patients. The transcriptional regulatory elements (TREs) of CEA include two enhancer elements and a promoter in the 5'-flanking region of the CEA gene. By using these elements in different combinations to control reporter gene expression and the replication of adenovirus variants in various tumor cells, we have identified an optimal CEA regulatory cassette that tightly controls gene expression and viral replication in CEA-producing colon cancer cells.