Survivin promoter-regulated oncolytic adenovirus with Hsp70 gene exerts effective antitumor efficacy in gastric cancer immunotherapy
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1 Department of Internal Medicine, No. 117 Hospital of Chinese PLA, Hangzhou 310004, China.
2 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
3 Department of Hepatobiliary Surgery, Fuzhou General Hospital of Nanjing Military Area, Fuzhou 350025, China
4 Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Changqing Su, email: [email protected]
Weiguo Wang, email: [email protected]
Weiguo Wang, Weidan Ji and Huanzhang Hu contributed equally to this work.
Keywords: Gastric cancer, Survivin gene, Heat shock protein, Oncolytic adenovirus, Gene therapy
Received: September 22, 2013 Accepted: December 12, 2013 Published: December 28, 2013
Gene therapy is a promising adjuvant therapeutic strategy for cancer treatment. To overcome the limitations of current gene therapy, such as poor transfection efficiency of vectors, low levels of transgene expression and lack of tumor targeting, the Survivin promoter was used to regulate the selective replication of oncolytic adenovirus in tumor cells, and the heat shock protein 70 (Hsp70) gene was loaded as the anticancer transgene to generate an AdSurp-Hsp70 viral therapy system. The efficacy of this targeted immunotherapy was examined in gastric cancer. The experiments showed that the oncolytic adenovirus can selectively replicate in and lyse the Survivin-positive gastric cancer cells, without significant toxicity to normal cells. AdSurp-Hsp70 reduced viability of cancer cells and inhibited tumor growth of gastric cancer xenografts in immuno-deficient and immuno-reconstruction mouse models. AdSurp-Hsp70 produced dual antitumor effects due to viral replication and high Hsp70 expression. This therapeutic system used the Survivin promoter-regulated oncolytic adenovirus vector to mediate targeted expression of the Hsp70 gene and ensure safety and efficacy for subsequent gene therapy programs against a variety of cancers.
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