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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Small Methods. 2022 Jan 17:e2100938. doi: 10.1002/smtd.202100938. Online ahead of print.ABSTRACTAs epithelial cells in the circulation are considered to originate from the tumor, the epithelial cell adhesion molecule has been commonly used as a standard marker for circulating tumor cells (CTCs) isolation. However, it seems to disappear after the epithelial-mesenchymal transition that most cancer cells undergo for intravasation. Thus, more advanced techniques for CTC detection are needed to better understand the clinical significance of CTCs. A cancer cell-specifically-infecting or replicating virus that codes a fluorescent...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
Sperm-associated antigen 9 (SPAG9) is closely related to the growth and metastasis of advanced prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase chemotherapy efficacy for advanced prostate cancer. Oncolytic adenovirus carrying a short hairpin RNA (shRNA) targeting SPAG9 (ZD55-shSPAG9) was applied alone or in combination with docetaxel in prostate cancer cells. Cells were analyzed by cell counting kit-8, Hocehst-33258, transwell and western blot analysis. For...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Pre-Clinical Reports Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
l B. Fisher Combining cancer-selective viral replication and simultaneous production of a therapeutic cytokine, with potent “bystander” anti-tumor activity, are hallmarks of the cancer terminator virus (CTV). To expand on these attributes, we designed a next generation CTV that additionally enables simultaneous non-invasive imaging of tumors targeted for eradication. A unique tripartite CTV “theranostic” adenovirus (TCTV) has now been created that employs three distinct promoters to target virus replication, cytokine production and imaging capabilities uniquely in cancer cells. Conditional repli...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Human Gene Therapy - Category: Genetics & Stem Cells Authors: Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Chemotherapy - Category: Cancer & Oncology Source Type: research
Standard-of-care treatment for malignant mesothelioma could change significantly, depending upon the results of an upcoming clinical trial of two immunotherapy agents used in combination with chemotherapy. The mesothelioma clinical trial will involve pembrolizumab, also known by the brand name Keytruda, and its synergy with ONCOS-102, a lesser-known, genetically modified adenovirus. Individually, both have shown modest efficacy for mesothelioma patients when used with chemotherapy. Together, there is potential for a much greater impact in significantly extending patient survival. The clinical trial is a partnership between...
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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
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