Prostate Cancer Gene Therapy Research Articles

New approaches and prospects of immunotherapy and gene therapy for prostate cancer

Prostate cancer stands as the most prevalent cancer globally, constituting 21% of all cancer diagnoses in male patients. Urgent optimization of prostate cancer care is essential, given that this disease claims 345,000 lives every year. These innovative approaches hold substantial promise for both researchers and patients, representing a beacon of hope in the inhibitory act against prostate cancer. Prostate cancer's gradual advancement deems it suitable for immune therapy, but trials in metastatic cases show limited effectiveness, likely due to compromised immunity. Hindered by defective cellular responses, an immune-suppressive microenvironment, emerging evidence and breakthroughs, such as CAR-T therapy, inspire cautious optimism for advanced prostate cancer immunotherapy. Tumors utilize tactics to escape immune recognition, promoting the proliferation of MDSCs, Treg cells, and TAMs. Immunotherapy targets prostate cancer by mostly expressed target proteins and overexpressed target proteins. Immune cells play a role in tumor development and metastasis in advanced prostate cancer. Modulating the tumor microenvironment presents therapeutic possibilities. Certain prostate cancer types exhibit potential responses to immune checkpoint inhibitors, yet obstacles remain, necessitating additional research for enhanced efficacy. Immunotherapy faces hurdles in prostate cancer—limited inflammation, scarce antigens, and a resistant microenvironment. Grasping resistance intricacies is pivotal. The identification of DNA's helical structure propelled global progress in disease treatment through gene therapy. Choosing gene therapy vectors is critical; viruses are potent but toxic, while nonviral options, though less toxic, encounter barriers affecting transfection. In the realm of prostate cancer treatment, immunotherapy and gene therapy are emerging as increasingly viable options.

Genetic Therapy Revolutionizing Prostate Cancer Treatment: A Comprehensive Analysis of Therapeutic Advancements

Prostate cancer remains a significant global health concern, demanding innovative and effective treatment strategies. In this era of precision medicine, gene therapy has emerged as a groundbreaking approach for the management of prostate cancer. This article provides a comprehensive review of the state-of-the-art research on the application of genetic therapy in the treatment of prostate cancer. We delve into the molecular underpinnings of prostate cancer and the intricate web of genetic alterations that drive its progression. Furthermore, we explore the diverse arsenal of genetic tools, such as CRISPR-Cas9, viral vectors, and RNA interference, which are being harnessed to target and modify prostate cancer-related genes. The article highlights the promise of gene therapy in enhancing treatment outcomes, minimizing side effects, and circumventing therapeutic resistance. Additionally, we discuss the current challenges, ethical considerations, and regulatory aspects surrounding the clinical translation of gene therapy for prostate cancer. Ultimately, this review underscores the transformative potential of genetic therapy in revolutionizing the management of prostate cancer and improving the quality of life for affected individuals.

Nanotherapeutic Approach to Delivery of Chemo- and Gene Therapy for Organ-Confined and Advanced Castration-Resistant Prostate Cancer.

Treatments for late-stage prostate cancer (CaP) have not been very successful. Frequently, advanced CaP progresses to castration-resistant prostate cancer (CRPC), with 50#37;-70% of patients developing bone metastases. CaP with bone metastasis-associated clinical complications and treatment resistance presents major clinical challenges. Recent advances in the formulation of clinically applicable nanoparticles (NPs) have attracted attention in the fields of medicine and pharmacology with applications to cancer and infectious and neurological diseases. NPs have been rendered biocompatible, pose little to no toxicity to healthy cells and tissues, and are engineered to carry large therapeutic payloads, including chemo- and genetic therapies. Additionally, if required, targeting specificity can be achieved by chemically coupling aptamers, unique peptide ligands, or monoclonal antibodies to the surface of NPs. Encapsulating toxic drugs within NPs and delivering them specifically to their cellular targets overcomes the problem of systemic toxicity. Encapsulating highly labile genetic therapeutics such as RNA within NPs provides a protective environment for the payload during parenteral administration. The loading efficiencies of NPs have been maximized while the controlled their therapeutic cargos has been released. Theranostic ("treat and see") NPs have developed combining therapy with imaging capabilities to provide real-time, image-guided monitoring of the delivery of their therapeutic payloads. All of these NP accomplishments have been applied to the nanotherapy of late-stage CaP, offering a new opportunity for a previously dismal prognosis. This article gives an update on current developments in the use of nanotechnology for treating late-stage, castration-resistant CaP.

Suggesting Tissue-Specific MSMB Gene Promoter as a Novel Approach for Prostate Targeted Gene Therapy.

Background and aim:Prostate cancer is the second most common cancer among men that has affected their quality of life. This study aimed to find prostate tissue-specific genes using bioinformatics methods to specifically target prostate cells in case of metastasis to other tissues. Materials and Methods:In this study, after finding a specific gene (MSMB) that is highly expressed in cancer, the optimal promoter region of this gene was isolated and inserted in an expression vector. Then, this vector was transfected into two prostate cancer cell lines (DU145 and LNCaP) and three non-prostate cell lines (LX-2, MRC-5, and U87) using the PEI chemical method. The expression of this vector in these cells was examined using fluorescent microscopy and flow cytometry. Results:We observed that the expression of MSMB promoter in DU145 cell line has a much higher activity than the CMV promoter, which is a ubiquitous promoter. The MSMB promoter didn’t show any activity in cells other than that of prostate derived cell lines. Conclusion:MSMB gene promoter with specific expression and high efficiency in prostate tissue compared to CMV promoter can play an essential role in gene therapy of prostate cancer.

Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene

Perforin secreted from cytotoxic lymphocytes plays a critical role in cancer immunosurveillance. The aim of this study was to investigate the therapeutic potential of liposomes containing perforin expression vector driven by the promotor of prostate-specific antigen (PSA). The anti-tumor effect of perforin was analyzed using prostate cancer (PC) PC-3 cells in which perforin expression was controlled by Tet-on system (PC-3PRF cells). Liposomes encapsulating PSA promoter-driven perforin expression vector (pLipo) were constructed for its specific expression in PC. The anti-tumor effect of pLipo was evaluated in vitro using docetaxel-resistant PC 22Rv1 PC cell line, 22Rv1DR, and PC-3 cells in the presence of human peripheral blood mono nuclear cells (PBMCs) and also in vivo using male nude mice bearing 22Rv1DR cell-derived tumor xenograft. Induction of perforin significantly inhibited growth of PC-3PRF cells. Treatment with pLipo induced perforin expression in 22Rv1DR cells expressing PSA but not in PC-3 cells lacking it. Treatment with pLipo at a low concentration was prone to inhibit growth of both cell lines and significantly inhibited growth of 22Rv1DR cells when co-incubated with PBMCs. The combined use of pLipo at a high concentration with PBMCs showed nearly complete inhibition of 22Rv1DR cell growth. Intravenous administration of pLipo via tail vein increased the level of perforin in tumor and serum and significantly decreased the tumor volume. Our results suggest that liposome-mediated PC-specific expression of perforin could be a novel therapy for advanced PC.

Bee Venom Components as Therapeutic Tools against Prostate Cancer.

Prostate cancer is one of the most common cancers in men. Despite the development of a variety of therapeutic agents to treat either metastatic hormone-sensitive prostate cancer, advanced prostate cancer, or nonmetastatic/metastatic castration-resistant prostate cancer, the progression or spread of the disease often cannot be avoided. Additionally, the development of resistance of prostate cancer cells to available therapeutic agents is a well-known problem. Despite extensive and cost-intensive research over decades, curative therapy for metastatic prostate cancer is still not available. Therefore, additional therapeutic agents are still needed. The animal kingdom offers a valuable source of natural substances used for the treatment of a variety of diseases. Bee venom of the honeybee is a mixture of many components. It contains proteins acting as enzymes such as phospholipase A2, smaller proteins and peptides such as melittin and apamin, phospholipids, and physiologically active amines such as histamine, dopamine, and noradrenaline. Melittin has been shown to induce apoptosis in different cancer cell lines, including prostate cancer cell lines. It also influences cell proliferation, angiogenesis, and necrosis as well as motility, migration, metastasis, and invasion of tumour cells. Hence, it represents an interesting anticancer agent. In this review article, studies about the effect of bee venom components on prostate cancer cells are discussed. An electronic literature research was performed utilising PubMed in February 2021. All scientific publications, which examine this interesting subject, are discussed. Furthermore, the different types of application of these promising substances are outlined. The studies clearly indicate that bee venom or melittin exhibited anticancer effects in various prostate cancer cell lines and in xenografts. In most of the studies, a combination of bee venom or the modified melittin with another molecule was utilised in order to avoid side effects and, additionally, to target selectively the prostate cancer cells or the surrounding tissue. The studies showed that systemic side effects and unwanted damage to healthy tissue and organs could be minimised when the anticancer drug was not activated until binding to the cancer cells or the surrounding tissue. Different targets were used, such as the matrix metalloproteinase 2, hormone receptors expressed by prostate cancer cells, the extracellular domain of PSMA, and the fibroblast activation protein occurring in the stroma of prostate cancer cells. Another approach used loaded phosphate micelles, which were cleaved by the enzyme secretory phospholipase A2 produced by prostate cancer cells. In a totally different approach, targeted nanoparticles containing the melittin gene were used for prostate cancer gene therapy. By the targeted nonviral gene delivery, the gene encoding melittin was delivered to the prostate cancer cells without systemic side effects. This review of the scientific literature reveals totally different approaches using bee venom, melittin, modified melittin, or protoxin as anticancer agents. The toxic agents acted through several different mechanisms to produce their anti-prostate cancer effects. These mechanisms are not fully understood yet and more experimental studies are necessary to reveal the complete mode of action. Nevertheless, the researchers have conducted pioneering work. Based on these results, further experimental and clinical studies about melittin and modifications of this interesting agent deriving from nature are necessary and could possibly lead to a complementary treatment option for prostate cancer.

Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer

ObjectiveCytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). MethodsFour high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n=3) or without neoadjuvant therapy (NT, n=4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. ResultsssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of single-stranded DNA (ssDNA) LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ=0.656, p<0.0001) as well as CD4+ T cells and CD20+ B cells (ρ=0.644, p<0.0001) in PCa with GT. ConclusionsEnhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.

Gene Therapy for Prostate Cancer: A Review.

According to the American Cancer Society, prostate cancer ranks second in terms of mortality and is a front-runner of newly detected cases. Conventional therapies neither eradicated cancer nor increased the life expectancy of patients obviating the need for less toxic as well as efficient therapies to treat cancer. Gene therapy alone, or in combination with conventional therapies, possesses a strong potential to combat cancer. This review encompasses a brief note on the etiology and conventional therapy of prostate cancer with an emphasis on gene therapy and its suitability for the treatment of prostate cancer. A comprehensive range of gene therapy approaches have been successfully explored for prostate cancer treatment in animal models and this has been well translated into early clinical trials. We have also discussed in brief about specific therapeutic genes and suitable vector systems for gene therapy in prostate cancer. Based on the results of these clinical trials, the application of gene therapy in prostate cancer therapeutics can be satisfactorily established.

ZIF-C for targeted RNA interference and CRISPR/Cas9 based gene editing in prostate cancer.

Gene therapy is highly suited for prostate cancer (PC). Metal-organic-frameworks (MOFs) are potential gene delivery systems. Target-specific cytoplasmic and nuclear knockdown in host gene expression using ZIF-C is shown for the first time through RNAi and CRISPR/Cas9 based gene editing in PC cells. A green tea phytochemical coating enhances intracellular delivery.

Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro.

Different types of siRNA delivery vehicles including nanoparticles have been synthesized and utilized for prostate cancer gene therapy. However, one of the most common limitations being faced is the toxicity of cationic polymers toward the cells. In the current study, magnetic nanoparticles were prepared and conjugated with cationic polymer, polyethylenimine. Then polyethylene glycol was conjugated with polyethylenimine to improve the biocompatibility of nanoparticles. The transmission electron microscopy size of nanoparticles was found to be 15.82 (±9.07) nm, while hydrodynamic size was about 79.20 (±0.68) nm. Zeta potential analysis of polyethylenimine and polyethylene glycol-coated nanoparticles was +31.4 (±0.62) and +5.65 (±0.76) mV, respectively. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed the presence of polyethylene glycol and polyethylenimine polymers in magnetic nanoparticles. Cell viability test in mouse fibroblast NIH 3T3 and prostate cancer PC3 cells showed an increased in biocompatibility of functionally modified polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles. siRNA targeting a disintegrin and metalloproteinase 10 (ADAM10) was successfully loaded into the polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles and delivered to PC3 cells. The results clearly demonstrated a significant decrease in cell viability, which increased within a certain siRNA concentration. The inhibitory concentration (IC50) value for ADAM10 siRNA was calculated to be 15.83 nM after 72 h. Confocal microscopy confirmed the delivery of siRNA-loaded nanoparticles intracellularly to the tumor cells cytosol. This magnetic system can be used as a powerful platform to inhibit cancer cells progression.

1001 - Investigation of gene therapy for prostate cancer by the JC virus-like particles delivering a PSA promoter driven-suicide gene

1001 - Investigation of gene therapy for prostate cancer by the JC virus-like particles delivering a PSA promoter driven-suicide gene

Osteonectin Promoter-Mediated Suicide Gene Therapy of Prostate Cancer.

Suicide gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene, combined with the prodrug ganciclovir (GCV) medication, is a promising approach for the treatment of malignant tumors, including prostate cancer. The success of this therapeutic strategy requires tissue- or tumor-specific gene expression and efficient gene delivery. In this chapter, we describe the experimental protocols of key methodologies, including promoter construction, reporter assay, adenoviral vector construction and preparation, HSV-tk enzymatic assay and cytotoxicity assay to evaluate the specificity and efficacy of osteonectin promoter-mediated HSV-tk/GCV suicide gene therapy of prostate cancer.

Peptide T7-modified polypeptide with disulfide bonds for targeted delivery of plasmid DNA for gene therapy of prostate cancer.

BackgroundVectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa).MethodsThe structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7–plasmid DNA complex were examined.ResultsThe results demonstrated that the CRD-PEG-T7–plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG–plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system.ConclusionThe results above indicatd that the CRD-PEG-T7–plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor.

Targeted nonviral gene therapy in prostate cancer.

Prostate cancer is the second-most widespread cancer in men worldwide. Treatment choices are limited to prostatectomy, hormonal therapy, and radiotherapy, which commonly have deleterious side effects and vary in their efficacy, depending on the stage of the disease. Among novel experimental strategies, gene therapy holds great promise for the treatment of prostate cancer. However, its use is currently limited by the lack of delivery systems able to selectively deliver the therapeutic genes to the tumors after intravenous administration without major drawbacks. To remediate this problem, a wide range of nonviral delivery approaches have been developed to specifically deliver DNA-based therapeutic agents to their site of action. This review provides an overview of the various nonviral delivery strategies and gene therapy concepts used to deliver therapeutic DNA to prostate cancer cells, and focuses on recent therapeutic advances made so far.

Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL, and interleukin-12

The possibility of using gene therapy for the treatment of prostate cancer is limited by the lack of intravenously administered delivery systems able to safely and selectively deliver therapeutic genes to tumors. Given that lactoferrin (Lf) receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of Lf to generation 3-diaminobutyric polypropylenimine dendrimer would improve its transfection and therapeutic efficacy in prostate cancer cells. In this study, we demonstrated that the intravenous administration of Lf-bearing DAB dendriplexes encoding TNFα resulted in the complete suppression of 70% of PC-3 and 50% of DU145 tumors over one month. Treatment with DAB-Lf dendriplex encoding TRAIL led to tumor suppression of 40% of PC-3 tumors and 20% of DU145 tumors. The treatment was well tolerated by the animals. Lf-bearing generation 3-polypropylenimine dendrimer is therefore a highly promising delivery system for non-viral gene therapy of prostate cancer.

Improving adenoviral vectors and strategies for prostate cancer gene therapy

Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.

Targeting strategies of adenovirus‑mediated gene therapy and virotherapy for prostate cancer (Review).

Prostate cancer (PCa) poses a high risk to older men and it is the second most common type of male malignant tumor in western developed countries. Additionally, there is a lack of effective therapies for PCa at advanced stages. Novel treatment strategies such as adenovirus-mediated gene therapy and virotherapy involve the expression of a specific therapeutic gene to induce death in cancer cells, however, wild-type adenoviruses are also able to infect normal human cells, which leads to undesirable toxicity. Various PCa-targeting strategies in adenovirus-mediated therapy have been developed to improve tumor-targeting effects and human safety. The present review summarizes the relevant knowledge regarding available adenoviruses and PCa-targeting strategies. In addition, future directions in this area are also discussed. In conclusion, although they remain in the early stages of basic research, adenovirus-mediated gene therapy and virotherapy are expected to become important therapies for tumors in the future due to their potential targeting strategies.

Towards prostate cancer gene therapy: Development of a chlorotoxin-targeted nanovector for toxic (melittin) gene delivery

Prostate cancer is the second leading cause of death due to cancer in men. Owing to shortcomings in the current treatments, other therapies are being considered. Toxic gene delivery is one of the most effective methods for cancer therapy. Cationic polymers are able to form stable nanoparticles via interaction with nucleic acids electrostatically. Branched polyethylenimine that contains amine groups has notable buffering capacity and the ability to escape from endosome through the proton sponge effect. However, the cytotoxicity of this polymer is high, and modification is one of the applicable strategies to overcome this problem. In this study, PEI was targeted with chlorotoxin (CTX) via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) cross-linker. CTX can bind specifically to matrix metalloproteinase-2 that is overexpressed in certain cancers. Melittin as the major component of bee venom has been reported to have anti-cancer activity. This was thus selected to deliver to PC3 cell line. Flow cytometry analysis revealed that transfection efficiency of targeted nanoparticles is significantly higher compared to non-targeted nanoparticles. Targeted nanoparticles carrying the melittin gene also decreased cell viability of PC3 cells significantly while no toxic effects were observed on NIH3T3 cell line. Therefore, CTX-targeted nanoparticles carrying the melittin gene could serve as an appropriate gene delivery system for prostate and other MMP-2 positive cancer cells.

Autoregulated expression of p53 from an adenoviral vector confers superior tumor inhibition in a model of prostate carcinoma gene therapy

ABSTRACTAlternative treatments for cancer using gene therapy approaches have shown promising results and some have even reached the marketplace. Even so, additional improvements are needed, such as employing a strategically chosen promoter to drive expression of the transgene in the target cell. Previously, we described viral vectors where high-level transgene expression was achieved using a p53-responsive promoter. Here we present an adenoviral vector (AdPGp53) where p53 is employed to regulate its own expression and which outperforms a traditional vector when tested in a model of gene therapy for prostate cancer. The functionality of AdPGp53 and AdCMVp53 were compared in human prostate carcinoma cell lines. AdPGp53 conferred greatly enhanced levels of p53 protein and induction of the p53 target gene, p21, as well as superior cell killing by a mechanism consistent with apoptosis. DU145 cells were susceptible to induction of death with AdPGp53, yet PC3 cells were quite resistant. Though AdCMVp53 was shown to be reliable, extremely high-level expression of p53 offered by AdPGp53 was necessary for tumor suppressor activity in PC3 and DU145. In situ gene therapy experiments revealed tumor inhibition and increased overall survival in response to AdPGp53, but not AdCMVp53. Upon histologic examination, only AdPGp53 treatment was correlated with the detection of both p53 and TUNEL-positive cells. This study points to the importance of improved vector performance for gene therapy of prostate cancer.

Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer

Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice.