Effect of a novel DNA vaccine on angiogenesis and tumor growth in vivo.
OBJECTIVE
To develop a DNA cancer vaccine that targets the vascular endothelial growth factor receptor.


METHODS
Mice were vaccinated intramuscularly with listeriolysin O-fetal liver kinase 1 (LLO-Flk1) or controls. Mice were also challenged subcutaneously with the tumor cell line TC-1. Tumor sizes were measured after vaccination. At the conclusion of the experiments, the tumors were harvested for immunohistochemical analysis and determination of hemoglobin content.


METHODS
Research laboratory.


METHODS
Six- to 8-week-old C57BL/6 mice.


METHODS
Fifty micrograms of each vector was administered 3 times at weekly intervals.


METHODS
Tumor size, mean vessel density of tumors, hemoglobin content of tumor.


RESULTS
Mice treated with the LLO-Flk1 vaccine experienced slower tumor growth relative to the other treatment groups. Complete tumor regression was observed in several cases. Immunohistochemical staining of tumors revealed fewer blood vessels in the mice vaccinated with the LLO-Flk1 vaccine relative to the other treatment groups. Finally, colorimetric assessment for hemoglobin suggested decreased vasculature in the tumor bed of these mice relative to the control groups.


CONCLUSIONS
The novel DNA cancer vaccine LLO-Flk1 can slow tumor growth in vivo.
McKinney
Kibwei A
KA
Department of Otorhinolaryngology, University of Pennsylvania School of Medicine, Philadelphia, USA.
Al-Rawi
Nada
N
Maciag
Paulo Cesar
PC
Banyard
Derek A
DA
Sewell
Duane A
DA
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology; D007150:Immunohistochemistry; D007167:Immunotherapy; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
D001427:Bacterial Toxins; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D006454:Hemoglobins; D006460:Hemolysin Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019444:Vaccines, DNA; D040301:Vascular Endothelial Growth Factor Receptor-2; C038705:hlyA protein, Listeria monocytogenes