Cancer medicine · 2026
Gene Therapy for Metastatic Castration-Resistant Prostate Cancer Using the JC Polyomavirus (JCPyV) Virus-Like Particles as a Gene Delivery Vector.
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Chou Chih-Chieh, Tseng Chih-En, Lin Yu-Shih, Wang Meilin, Chen Pei-Lain, Chang Deching, Shen Cheng-Huang, Fang Chiung-Yao
Аннотация
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.
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.