Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo

Molecular Cancer

Research

Kan Shifu¹  Tian Mingyao¹  Jin Kuoshi¹  Li Xiao¹  Wang Zhuoyue¹  Jin Ningyi¹  Li Chang¹  Wang Yuhang¹  Lu Huijun¹  Liu Yan²  Yang Encheng³  Xu Xiaohong³  Gao Pegn⁴  Wen Zhongmei⁵  Sun Lili⁶ 

[1] Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China;Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China;Department of Gastroenterology, the First Hospital of Jilin University, Changchun, China;Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China;Department of Gastroenterology, the First Hospital of Jilin University, Changchun, China;The Hospital of Digestive Diseases, Hospital of Heilongjiang Province, Harbin, China;Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China;Department of Hematology and Oncology, People's Hospital of Jilin Province, Changchun, China;Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China;Department of Respiratory Medicine, the First Hospital of Jilin University, Changchun, China;Head and Neck Surgery, The Tumor hospital of Jilin province, Changchun, China;

关键词: Recombinant Adenovirus;    Intratumoral Injection;    Cancer Gene Therapy;    hTERT Promoter;    Oncolytic Adenovirus;   

DOI  :  10.1186/1476-4598-9-10

 received in 2009-11-10, accepted in 2010-01-20,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials.ResultsThe observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The in vivo assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the in vitro studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival.ConclusionsThese data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.

【 授权许可】

Unknown   
© Xiao et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.