The enhanced anti-angiogenic and antitumor effects of combining flk1-based DNA vaccine and IP-10.
The purpose of the present study was to evaluate the anti-vasculature effects and the anti-tumor effects of attenuated Salmonella typhimurium vaccine strain encoding murine vascular endothelial growth factor (VEGF) receptor-2 (flk1) in combination with plasmid DNA vector encoding the murine interferon-induced protein of 10kDa (IP-10 or CXCL10) gene. Mouse models of malignant melanoma (B16-F10) were treated with combining orally given attenuated S. typhimurium vaccine strain encoding flk1 with direct intratumoral injection of a non-viral plasmid DNA vector encoding the murine IP-10 gene. The volumes of tumors and survival of mice bearing B16-F10 tumors were observed. Cytolytic T lymphocyte (CTL) response was measured by cytotoxic assay, vessel density and tumor-cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining. The results revealed the combination therapy groups showed more significantly inhibited tumor growth, apoptosis of tumor cells, and reduced neovascularization, cell proliferation, and developed a strong CTL response in these mice. In summary, the therapy of attenuated S. typhimurium vaccine strain encoding flk1 combined with the IP-10 gene has significant synergistic effect against tumors.
Lu
Xiao-ling
XL
Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Jiang
Xiao-bing
XB
Liu
Ru-en
RE
Zhang
Sheng-min
SM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D008546:Melanoma, Experimental / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D012486:Salmonella typhimurium / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; D054357:Chemokine CXCL10; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2