A combination of flk1-based DNA vaccine and an immunomodulatory gene (IL-12) in the treatment of murine cancer.
OBJECTIVE
The aim of this study was to investigate the antivasculature effects and the antitumor effects of combining attenuated Salmonella typhimurium vaccine strain encoding murine vascular endothelial growth factor (VEGF) receptor-2 (flk1) with plasmid DNA vector encoding the murine IL-12 (mIL-12) gene.


METHODS
Mouse models of Gl261 glioblastoma were treated with combining orally given attenuated Salmonella typhimurium vaccine strain encoding flk1 with direct intratumoral injection of a nonviral plasmid DNA vector encoding the murine IL-12 (mIL-12) gene. The volumes of tumors were observed. Cytolytic T lymphocyte (CTL) response was measured by a 4-hour 51Cr release assay, vessle density and tumor cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining.


RESULTS
Compared to mice receiving single agent therapy, received either oral immunization flk1-based vaccine only or the therapeutic gene-IL-12 plasmid DNA only or those in the control group, the combination therapy groups developed a strong CTL response and showed more significantly inhibited tumor growth, apoptosis of tumor cells, and reduced neovascularization and cell proliferation in these mice.


CONCLUSIONS
The therapy of attenuated Salmonella typhimurium vaccine strain encoding flk1 combined with the interleukin-12 gene has significant synergistic effect against tumors.
Keke
Feng
F
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. fengke1976@yahoo.com.cn
Hongyang
Zhao
Z
Hui
Qiu
Q
Jixiao
Liu
L
Jian
Chen
C
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy*; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic; D010957:Plasmids / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D019444:Vaccines, DNA / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D019444:Vaccines, DNA; D018664:Interleukin-12; D004247:DNA; D040301:Vascular Endothelial Growth Factor Receptor-2