Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene.

Abstract

Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DNA virus. Its virus-like particles (VLPs) exhibit similar tropism to native virions and they are capable of delivering exogenous genes to the target cells for expression. JCPyV has been detected in prostate cells; therefore, prostate cancer cells may be susceptible to JCPyV infection and JCPyV VLPs may be used as a vector for gene therapy against prostate cancer. Here we constructed a plasmid (pPSAtk) that allows expression of the thymidine kinase suicide gene only in androgen receptor (AR) positive prostate cancer cells using the prostate-specific antigen (PSA) promoter, and used JCPyV VLPs as a vector to carry pPSAtk (PSAtk-VLPs) for transcriptional targeting in prostate cancer cells. In this study, we found that PSAtk-VLPs could only kill AR-positive CRPC 22Rv1 cells in vitro and inhibit the growth of tumor nodules in the xenograft mouse model. Our results reveal that PSAtk-VLPs could potentially be used as a new option for treating CRPC patients in the future.