Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer.
Survival after pancreatic cancer remains poor despite incremental advances in surgical and adjuvant therapy, and new strategies for treatment are needed. Oncolytic virotherapy is an attractive approach for cancer treatment. In this study, we have evaluated the effectiveness of the Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of vaccinia virus was effective against all human pancreatic carcinoma cells tested in vitro, especially those insensitive to oncolytic adenovirus. The virus displayed inherently high selectivity for cancer cells, sparing normal cells both in vitro and in vivo, with effective infection of tumors after both intravenous (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin-angiostatin fusion protein was confirmed in a pancreatic cancer model both in vitro and in vivo, with evidence of inhibition of angiogenesis. This novel vaccinia virus showed significant antitumor potency in vivo against the Suit-2 model by i.t. administration. This study suggests that the novel Lister strain of vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential therapeutic agent for pancreatic cancer.
Tysome
J R
JR
Centre for Molecular Oncology & Imaging, Institute of Cancer, Barts and the London School of Medicine and Dentistry, London, UK.
Briat
A
A
Alusi
G
G
Cao
F
F
Gao
D
D
Yu
J
J
Wang
P
P
Yang
S
S
Dong
Z
Z
Wang
S
S
Deng
L
L
Francis
J
J
Timiryasova
T
T
Fodor
I
I
Lemoine
N R
NR
Wang
Y
Y
D043168:Angiostatins / Q000235:genetics; D000818:Animals; D019677:Artificial Gene Fusion; D003131:Combined Modality Therapy; D043169:Endostatins / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays
D043169:Endostatins; D011993:Recombinant Fusion Proteins; D043168:Angiostatins