E1B-55kD-deleted oncolytic adenovirus armed with canstatin gene yields an enhanced anti-tumor efficacy on pancreatic cancer.
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-55kDa 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.
He
Xiao-Ping
XP
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Su
Chang-Qing
CQ
Wang
Xing-Hua
XH
Pan
Xue
X
Tu
Zhen-Xing
ZX
Gong
Yang-Fang
YF
Gao
Jun
J
Liao
Zhuan
Z
Jin
Jing
J
Wu
Hong-Yu
HY
Man
Xiao-Hua
XH
Li
Zhao-Shen
ZS
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D024141:Collagen Type IV / Q000096:biosynthesis / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014765:Viral Vaccines; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D017501:Adenovirus E1B Proteins; C502625:COL4A2 protein, human; D024141:Collagen Type IV; D010446:Peptide Fragments; D014765:Viral Vaccines; C464532:dl1520