DNA Vaccine Disrupts Angiogenesis and Blocks Tumor Growth

A novel anticancer vaccine targets a protein required for regulating development of the new blood vessels that tumors need to generate in order to grow and spread.

The protein, delta-like ligand 4' (DLL4), which is located in the growing tip cells of new blood vessels, was recently identified as a critical regulator of angiogenesis (new blood vessel formation). Capitalizing on this knowledge, investigators at the Karolinska Institutet (Stockholm, Sweden) prepared a vaccine based on a fragment of DNA that encodes part of the DLL4 molecule. The DNA in the form of plasmids was injected into mice with mammary carcinomas.

Results published in the May 24, 2010, online edition of the journal Oncogene revealed that incorporation of the plasmids by mouse cells resulted in production of DLL4 by the mice, which triggered an immune response against the protein. This immune response disrupted the formation of functional blood vessels and inhibited further growth of the tumors. Despite its effect on new blood vessel formation, the vaccine did not delay the wound healing response or generate any signs of the toxicity that might be associated with drugs that block DLL4 signaling.

"We have worked with breast cancer tumors since they often express high levels of DLL4, while normal breast tissue does not. We hope that it will be possible to use this vaccine to prevent recurrence of breast cancer after surgical treatment,” said senior author Dr. Kristian Pietras, associate professor of medical biochemistry and biophysics at the Karolinska Institutet.

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