Oncolytic herpesvirus with secretable angiostatic proteins in the treatment of human lung cancer cells.
BACKGROUND
The wild-type herpes simplex virus type 1 (HSV-1) has strong infectivity and cytolytic effect on almost all types of mammalian cells. Genetic engineering can now restrict this cytolysis to only malignant cells. G207 is an oncolytic HSV-1 vector developed based on this strategy.


METHODS
We used G207 as the backbone and integrated the exogenous endostatin-angiostatin fusion protein gene to generate a new vector, AE618.


RESULTS
Marked expressions of fusion protein in A549 and H460 lung cancer cells and culture medium were found 24 hours after treatment with AE618. In comparison with the G207 treatment group, the secreted protein from H460 cells treated with AE618 significantly inhibited the growth of human umbilical vein endothelial cells (HUVEC). AE618 also significantly inhibited the growth of xenografted tumors in vivo.


CONCLUSIONS
We propose that AE618 has the potential to be a novel anticancer agent with both oncolytic and anti-angiogenesis effects.
Yang
Cheng-Ta
CT
Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Lin
Yu-Chin
YC
Lin
Chun-Liang
CL
Lu
Jessica
J
Bu
Xuexian
X
Tsai
Ying-Huang
YH
Jia
William W G
WW
D043168:Angiostatins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics*; D042783:Endothelial Cells / Q000821:virology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D021382:Protein Sorting Signals / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D043169:Endostatins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D043168:Angiostatins