624. Conditionally Replicative Adenovirus Vector Overexpressing the ADP (E3-11.6K) Protein and Armed with Human Interferon Alpha
Year: 2006
Type: article
Abstract: We have previously reported on a tumor-specific conditionally replicating adenovirus vector named KD3 that overexpresses the E3-11.6K |[ldquo]|Adenovirus Death Protein|[rdquo]| (ADP). Overexpression of ADP increases vector spread within the tumors, enhancing oncolytic activity. The replication of this vector is restricted to cancer as opposed to normal cells due to mutations in the E1A protein that eliminate binding of E1A to pRB and p300. We have now constructed an improved version of KD3 that is armed with human interferon alpha (hIFN-|[alpha]|). KD3-IFN carries the hIFN-|[alpha]| cDNA in the E3 region downstream of the ADP gene. The vector retains the featureof ADP overexpression and expresses secreted and functionally active hIFN-|[alpha]| strictly at late stages of vector replication. Vectors KD3-DsRed and KD3-SEAP (encoding human secreted placental alkaline phosphatase) carrying reporter genes were also constructed and used to visualize (DsRed) or quantify (SEAP) expression levels in cell culture and in animal models. In cell culture, KD3-IFN had oncolytic activity similar to KD3, exceeding the oncolytic activity of dl1101/1107 (an adenovirus mutant with the same E1A mutation as KD3-IFN but with less ADP production). Therefore, the inclusion of the transgene did not compromise the functional manifestation of ADP overexpression, and high levels of hIFN-|[alpha]| did not adversely affect vector growth and spread.
Source: Molecular Therapy
Institutions: VirRx (United States), Saint Louis University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W2018237428