Comparison of prostate-specific promoters and the use of PSP-driven virotherapy for prostate cancer

Area of Science:

• Oncolytic virology
• Cancer gene therapy
• Prostate cancer research

Background:

• Prostate cancer is a leading cause of cancer death in men.
• Virus-based gene therapy shows promise but faces challenges with in vivo cellular transduction efficiency.
• Conditional oncolytic viruses (CRADs) aim to specifically target prostate cancer, minimizing systemic toxicity.

Purpose of the Study:

• To compare the specificity and activity of three prostate-specific promoters (PSA, probasin, MMTV LTR) in vitro and in vivo.
• To construct a prostate-specific oncolytic adenovirus (CRAD) using the most effective promoter.
• To evaluate the efficacy and specificity of the developed CRAD against prostate cancer cells in cell culture and animal models.

Main Methods:

• In vitro and in vivo analysis of three prostate-specific promoters (PSA, probasin, MMTV LTR).
• Development of a conditional replication adenovirus (CRAD) controlled by the adenoviral E1 region, utilizing the best-performing promoter.
• Assessment of CRAD efficacy and specificity in prostate cancer cell cultures and animal models (mice xenografts, canine models).

Main Results:

• Comparative analysis of PSA, probasin, and MMTV LTR promoters identified the most suitable candidate for prostate-specific targeting.
• Successful construction of a prostate-specific CRAD.
• Demonstration of CRAD's efficacy and specificity against prostate cancer in preclinical models.

Conclusions:

• The selection and incorporation of an optimal prostate-specific promoter are crucial for developing effective and targeted oncolytic adenoviruses.
• The developed prostate-specific CRAD shows potential as a targeted therapeutic strategy for advanced prostate cancer.
• Further research and development of CRADs hold promise for improving prostate cancer treatment outcomes with reduced side effects.