A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent...

Area of Science:

• Oncolytic virotherapy
• Gene therapy
• Molecular diagnostics

Background:

• Adenovirus serotype 5 (Ad5) is a common vector in cancer gene therapy and oncolytic virotherapy.
• Ad5 infectivity relies on coxsackie and adenovirus receptor (CAR) expression levels on target cells.
• Current methods for assessing CAR expression (flow cytometry, western blotting, IHC) have limitations.

Purpose of the Study:

• To develop a simple and effective system for detecting and assessing functional CAR expression in human tumor cells.
• To evaluate the utility of a green fluorescent protein (GFP)-expressing, telomerase-specific, replication-competent adenovirus (OBP-401) for this purpose.

Main Methods:

• Infection of human tumor cells and normal fibroblasts with OBP-401.
• Assessment of GFP expression as an indicator of CAR-mediated infection.
• Comparison of OBP-401's detection efficiency with conventional methods.
• Evaluation of OBP-401 in distinguishing CAR-positive tumor tissues from normal and CAR-negative tissues in biopsy samples.

Main Results:

• OBP-401 infection resulted in detectable GFP expression specifically in CAR-expressing tumor cells.
• GFP expression correlated significantly with CAR levels in tumor cells.
• OBP-401 demonstrated higher efficiency in detecting low CAR expression compared to conventional methods.
• OBP-401 successfully differentiated CAR-positive tumor tissues from CAR-negative tissues in biopsy samples.

Conclusions:

• GFP-expressing, telomerase-specific, replication-competent adenovirus (OBP-401) is a potent diagnostic tool.
• OBP-401 enables accurate assessment of functional CAR expression in tumor cells.
• This method is valuable for optimizing Ad5-based antitumor therapies.