DNA Vaccine Curbs Angiogenesis, Tumors in Mice
May provide an inexpensive alternative to angiostatin
THURSDAY, June 8 (HealthDay News) -- A DNA-based vaccine targeting the angiomotin receptor prevents angiogenesis and tumor growth in a mouse model and may provide an inexpensive alternative to angiogenesis inhibitors such as angiostatin, according to a report published online June 5 in the Proceedings of the National Academy of Sciences Early Edition.
Angiostatin has been shown to reduce tumor growth by targeting the angiomotin receptor and reducing angiogenesis, but requires frequent high-dose injections. In this study, Lars Holmgren, M.D., Ph.D., of the Karolinska Institute in Stockholm, Sweden, and colleagues used in vivo electroporation to introduce plasmid DNA encoding the angiomotin receptor into live mice, followed by an intramuscular injection to stimulate an immune response against the receptor.
The vaccinated mice produced antibodies against angiomotin that could prevent endothelial growth in cultured endothelial cells, an effect previously shown with angiostatin treatment. In addition, the vaccine prevented tumor growth in 12 of 18 mice for over 150 days and reduced angiogenesis in a matrigel tumor model system.
"We describe a strategy that circumvents the problems of low half-life in circulation and expensive production of the endogenous angiogenesis inhibitor angiostatin," the authors write. "Our report provides the rationale for targeting angiomotin to inhibit tumor angiogenesis, which may be achieved through either DNA vaccination or the use of therapeutic mAbs."
Funding was provided in part by BioInvent International, Lund, Sweden.