Ad5/35E1aPSESE4: A novel approach to marking circulating prostate tumor cells with a replication competent adenovirus controlled by PSA/PSMA transcription regulatory elements

Circulating tumor cells serve as useful biomarkers with which to identify disease status associated with
survival, metastasis and drug sensitivity. Here, we established a novel application for detecting PSA/
PSMA-positive prostate cancer cells circulating in peripheral blood employing an adenovirus called Ad5/
35E1aPSESE4. Ad5/35E1aPSESE4 utilized PSES, a chimeric enhancer derived from PSA/PSMA promoters
that is highly active with and without androgen. A fluorescence signal mediated by GFP expression upon
Ad5/35E1aPSESE4 infection was selectively amplified in PSA/PSMA-positive prostate cancer cells in vitro
and ex vivo. Furthermore, for the in vivo model, blood drawn from TRAMP was tested for CTCs with Ad5/
35E1aPSESE4 infection and was positive for CTCs at week 16. Validation was performed on patient blood
at various clinical stages and found out 1–100 CTCs expressing GFP upon Ad5/35E1aPSESE4 infection.
Interestingly, CTC from one patient was confirmed to be sensitive to docetaxel chemotherapeutic reagent
and to abundantly express metastasis-related genes like MMP9, Cofilin1, and FCER1G through RNA-seq.
Our study established that the usage of Ad5/35E1aPSESE4 is effective in marking PSA/PSMA-positive prostate
cancer cells in patient blood to improve the efficacy of utilizing CTCs as a biomarker.