Oncolytic Herpesvirus with Secretable Angiostatic Proteins in the Treatment of Human Lung Cancer Cells

• Published in: Anticancer research 2005-05, Vol.25 (3B), p.2049-2054
• Main Authors: YANG, Cheng-Ta, LIN, Yu-Chin, LIN, Chun-Liang, LU, Jessica, XUEXIAN BU, TSAI, Ying-Huang, JIA, William W.-G
• Format: Article
• Language: English
• Subjects: Angiostatins - biosynthesis; Angiostatins - genetics; Animals; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - therapy; Carcinoma, Non-Small-Cell Lung - virology; Cell Line, Tumor; Endostatins - biosynthesis; Endostatins - genetics; Endothelial Cells - virology; Genetic Therapy - methods; Genetic Vectors - genetics; Herpes simplex virus 1; Herpesvirus; Herpesvirus 1, Human - genetics; Humans; Interleukin-12 - genetics; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - therapy; Lung Neoplasms - virology; Medical sciences; Mice; Mice, SCID; Pneumology; Protein Sorting Signals - genetics; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Tumors; Tumors of the respiratory system and mediastinum; Xenograft Model Antitumor Assays
• ISSN: 0250-7005; 1791-7530

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. Materials and 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. Conclusion: We propose that AE618 has the potential to be a novel anticancer agent with both oncolytic and anti-angiogenesis effects.