Survivin promoter-regulated oncolytic adenovirus with Hsp70 gene exerts effective antitumor efficacy in gastric cancer immunotherapy.
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.
Department of Internal Medicine, No. 117 Hospital of Chinese PLA, Hangzhou 310004, China.
Weiguo
W
Wang
Weidan
W
Ji
Huanzhang
H
Hu
Juming
J
Ma
Xiaoya
X
Li
Weiqun
W
Mei
Yang
Y
Xu
Huizhen
H
Hu
Yan
Y
Yan
Qizhe
Q
Song
Zhigang
Z
Li
Changqing
C
Su
D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D000077022:Survivin; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C117749:Birc5 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin