Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3‐CTV)

Abstract Few options are available for treating patients with advanced prostate cancer (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy could provide a viable option for this neoplasm. Conditionally replication‐competent adenoviruses (CRCAs) represent potentially useful reagents for treating prostate cancer (PC). We previously constructed a CRCA, Cancer Terminator Virus (CTV), which showed efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5‐background (Ad.5‐CTV) with infectivity depending on Coxsackie‐Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective Ad‐mediated therapy. Using serotype chimerism, a novel CTV (Ad.5/3‐CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber knob thereby facilitating infection in a CAR‐independent manner. We evaluated Ad.5/3‐CTV in comparison with Ad.5‐CTV in low CAR human PC cells, demonstrating higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3‐CTV potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a spontaneously induced PC that develops in Hi‐myc transgenic mice. Considering the significant responses in a Phase I clinical trial of a non‐replicating Ad.5‐mda‐7 in advanced cancers, Ad.5/3‐CTV may exert improved therapeutic benefit in a clinical setting. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: Original Research Article Source Type: research

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Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
Authors: Eremina NV, Kazey VI, Mishugin SV, Leonenkov RV, Pushkar DY, Mett VL, Gudkov AV Abstract Toll-like receptor 5 (TLR5) controls endogenous immune responses to pathogens and is a promising target for pharmacological stimulation of anti-tumor immunity. Mobilan is an innovative gene therapy agent consisting of a non-replicating bicistronic adenovirus directing constitutive expression of human Toll-like receptor 5 (TLR5) and the secreted flagellin-based TLR5 agonist, 502s. In mice, Mobilan injection into prostate tumors resulted in autocrine TLR5 signaling, immune system activation, and suppression of tumor grow...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
In conclusion, the combination of ionizing radiation and oncolytic adenovirus expressing IL24 could achieve synergistic anti-tumor effect on prostate cancer, and is a promising strategy for prostate cancer therapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: SIRT7 plays an important role in the development and progression of human PCa and may be a promising prognostic marker for prostate cancer. PMID: 32019578 [PubMed - in process]
Source: Clinical Prostate Cancer - Category: Cancer & Oncology Authors: Tags: J Exp Clin Cancer Res Source Type: research
Condition:   Adenocarcinoma of the Prostate Intervention:   Biological: ORCA-010 Sponsors:   Orca Therapeutics B.V.;   CMX Research Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Xu SG, Yu JJ, Shi Q, Niu Q, Guo Z, Guo BY, Zhou GC, Gu X, Wu YX Abstract The present study aimed to construct conditionally replicative adenovirus (CRAds) carrying small hairpin (sh)RNA targeting enhancer of zeste homolog 2 (EZH2), in order to study its effect on inhibiting prostate cancer (PCa) cell growth and invasion. Immunohistochemical analyses of EZH2 was performed in tumor tissue samples from PCa and benign prostate hyperplasia (BPH). The human telomerase reverse transcriptase (hTERT) promoter was chosen to transcriptionally control EZH2 gene expression to obtain adenoviral replication (Ad‑hTERT...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Herein we demonstrate that ultraviolet light–inactivated Herpes Simplex Virus-1 (UV-HSV-1) stimulates peripheral blood mononuclear cells (PBMCs) to lyse both androgen-sensitive and androgen-independent prostate cancer (PrCA) cell lines, but not the benign prostatic hyperplastic epithelial cell line, BPH-1, and is 1000–10,000-fold more potent at stimulating this killing than ultraviolet light-inactivated Vesicular Stomatitis Virus, adenovirus, reovirus or cytomegalovirus. Among PBMCs, natural killer (NK) cells appear to be a major cell type involved in this killing and UV-HSV-1 appears to directly and potently s...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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