Gene Therapy for Metastatic Castration‐Resistant Prostate Cancer Using the
JC
Polyomavirus (
JCPyV
) Virus‐Like Particles as a Gene Delivery Vector
Chih‐Chieh Chou, Chih‐En Tseng, Yu‐Shih Lin, Meilin Wang, Pei‐lain Chen, Deching Chang, Cheng‐Huang Shen, Chiung‐Yao Fang ABSTRACT
Background
Systemic metastasis remains the leading cause of mortality in patients with advanced prostate cancer, particularly in castration‐resistant prostate cancer (CRPC), for which effective systemic therapeutic options are limited. Gene therapy is a potential strategy for achieving selective tumor targeting and systemic disease control in metastatic settings. This study aimed to establish a systemic metastasis animal model for CRPC and evaluate the therapeutic efficacy of JC polyomavirus (JCPyV) virus‐like particle (VLPs)–based gene therapy against metastatic disease.
Methods
A near‐infrared fluorescent protein (iRFP)‐expressing CRPC cell line was used to establish a systemic metastasis model by tail‐vein injection in mice. The therapeutic efficacy of JCPyV VLPs carrying a prostate‐specific antigen (PSA) promoter‐driven suicide gene (PSAtk‐VLPs), administered in combination with ganciclovir (GCV), was evaluated longitudinally by fluorescence molecular tomography (FMT), with enzalutamide/leuprorelin acetate (ENZ/LEU) included as a clinical treatment comparator.
Results
CRPC metastases in the lungs, liver, spleen, kidneys, and bones were detected by FMT in real time. Control mice exhibited exponential CRPC growth, whereas ENZ/LEU treatment delayed CRPC progression. PSAtk‐VLPs/GCV significantly inhibited the growth of metastatic CRPC. However, no significant differences in survival were observed among the MOCK, ENZ/LEU, and PSAtk‐VLP/GCV groups (log‐rank test, p = 0.7351).
Conclusion
These findings support that JCPyV‐derived virus‐like particles constitute a promising therapeutic approach for metastatic CRPC, enabling systemic delivery of suicide gene therapy with selective inhibition of tumor growth and translational relevance.