Antitumor effects of oncolytic adenovirus armed with PSA-IZ-CD40L fusion gene against prostate cancer

Advanced prostate cancer (PC) still remains incurable. Novel immunogene therapy shows promise as treatment strategy that can target both localized and metastasized PC. In this study, we have developed a PC-specific oncolytic adenovirus (Ad-PL-PPT-E1A) armed with fusion gene of prostate-specific antigen and CD40 ligand, and aimed to evaluate its therapeutic effect in vitro and in vivo. After they were rescued in human embryonic kidney 293 cells, we confirmed that Ad-PL-PPT-ElA could mediate the expression of El A efficiently and produce abundant progeny viruses in PC cells in vitro. Our data showed that Ad-PL-PPT-ElA induced apoptosis and resulted in specific oncolytic toxicity in PC cells, which was detected by Annexin-V staining and crystal violet, respectively. After stimulation with lysates, immune phenotypes and cytokines expression of human dendritic cells was detected by flow cytometry and real-time polymerase chain reaction, respectively. And, the results showed that the lysate of Ad-PL-PPT-ElA infected LNCaP cells upregulated the expression of CD80, CD83, CD86 and mRNA level of interleukin-6 (IL-6), IL-12,1L-23 and tumor necrosis factor-a significantly. In established PC3M cell-xenografted mouse models, Ad-PL-PPT-ElA treatment improved the survival and suppressed the tumor growth obviously. In conclusion, Ad-PL-PPT-ElA exhibited enhanced antitumor activity is a promising approach for gene therapy of advanced PC.