E1B-55kD-deleted oncolytic adenovirus armed with canstatin gene yields an enhanced anti-tumor efficacy on pancreatic cancer

Abstract Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55 kDa gene for selective replication in tumor cells, as well as carrying a ne...

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Bibliographic Details
Published in:Cancer letters 2009-11, Vol.285 (1), p.89-98
Main Authors: He, Xiao-Ping, Su, Chang-Qing, Wang, Xing-Hua, Pan, Xue, Tu, Zhen-Xing, Gong, Yang-Fang, Gao, Jun, Liao, Zhuan, Jin, Jing, Wu, Hong-Yu, Man, Xiao-Hua, Li, Zhao-Shen
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
Adenovirus
Adenovirus E1B Proteins - genetics
Angiogenesis
Animals
Anti-angiogenesis
Apoptosis
Cancer therapies
Canstatin
Cell culture
Cell growth
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cloning
Collagen Type IV - biosynthesis
Collagen Type IV - genetics
Gene Deletion
Gene therapy
Genes
Hematology, Oncology and Palliative Medicine
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Oncolytic adenovirus
Oncolytic Virotherapy
Oncolytic Viruses - genetics
Oncolytic Viruses - metabolism
Pancreas
Pancreatic cancer
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
Pancreatic Neoplasms - virology
Peptide Fragments - biosynthesis
Peptide Fragments - genetics
Plasmids
Proteins
Time Factors
Tumors
Viral Vaccines
Virus Replication
Viruses
Xenograft Model Antitumor Assays
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Summary:Abstract Conditionally-replicating adenovirus (CRAd) therapy is currently being tested against pancreatic cancer and has shown some promise. To improve the efficacy, a novel virus CRAd-Cans was designed by deletion of E1B-55 kDa gene for selective replication in tumor cells, as well as carrying a new angiogenesis inhibitor gene, canstatin . CRAd-Cans mediated higher expression of canstatin in BxPC-3 pancreatic cancer cell line compared to the replication-deficient adenovirus Ad5-Cans. The modified CRAd-Cans manifested the same selective replication and cytocidal effects in pancreatic cancer cells as ONYX-015 in vitro , yet showed greater reduction of tumor growth in nude mice with markedly prolonged survival rate in vivo ( P < 0.05), compared to that of either ONYX-015 or Ad5-Cans. Pathological examination revealed viral replication, decreased microvessel density and increased cancer cell apoptosis in CRAd-Cans-treated xenografts. The results suggest that the novel oncolytic virus CRAd-Cans, showing synergistic effects of oncolytic therapy and anti-angiogenesis therapy, is a new promising therapeutics for pancreatic cancer.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.05.006