A Novel Method for Determining the Level of Viable Disseminated Prostate Cancer Cells
Abstract
This project seeks to determine whether conditionally replicating adenovirus (CRAd) reporters can be exploited to detect viable and tissue-specific circulating tumor cells in the blood of patients with localized or metastatic prostate cancer. The approach specifically applies secreted reporters that are expressed under the control of the adenovirus Major Late Transcriptional Unit (MLTU) to limit reporter expression to only those cells in which the CRAd has replicated and to separate the secreted reporter signal from the complex mixture of cells in human blood. In this first year of the project several candidate Circulating Tumor Cell Reporter Vectors (CTC-RVs) have been generated and characterized. These reporter vectors have replication which is restricted to Androgen Receptor (AR) positive prostate cancer cells through regulation of the early viral E1A gene by the ARresponsive and prostate-selective probasin promoter. Reporter activity from these viruses was confirmed to be expressed and secreted into the media. Initial conditions for CTC-RV infection have been established and preliminary results indicate that the level of reporter activity correlates with the number of prostate cancer cells. Cell dilution studies demonstrate that this approach can detect CTCs at levels comparable to alternative CTC-detection strategies. The selectivity for prostate cancer cells has also been demonstrated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA569676
Entities
People
- Shawn E Lupold
Organizations
- Johns Hopkins University