Directed Gene Therapy Shuts Down Tumor Angiogenesis

Cationic nanoparticles bound to a mutant Raf gene, ATPµ-Raf, which blocks endothelial signaling and angiogenesis in response to multiple growth factors, were successfully used to treat cancer in mice by preventing the tumors from producing new blood vessels. This study was published in the June 28, 2002, issue of Science.

Investigators from Scripps Research Institute (La Jolla, CA, USA) conjugated an angiogenisis suppressing gene with a 50-100 nanometer-sized particle that selectively targets the cells that form new blood vessels in cancer tumors. This combination of gene delivery with specific vascular targeting effectively disrupted the blood supply of tumors in mice without influencing the normal blood vessels or any other tissue.

Antiangiogenic treatments have been studied for many years, but this anticancer nanoparticle represents a novel approach. Unlike systemic angiogenesis blockers, which become diffused throughout the blood steam upon injection, the nanoparticle-targeting vehicle directs itself to areas of the body where the tumors exist and where local vascular cells are expanding to form new blood vessels. The nanoparticle targets these cells and deposits multiple copies of a gene that effectively blocks angiogenesis and kills tumors.

"We saw strong regression of large tumors in every system we looked at,” said Scripps Immunology Professor David Cheresh, who led the study.

The investigators say that the next step will be to refine the technique as a general approach towards cancer therapy. The method might prove efficacious along with some existing chemotherapy, for instance, and thereby reduce the toxicity of existing anticancer drugs. The nanoparticles may also be useful in several other diseases where angiogenesis plays a major role, such as heart disease, stroke, rheumatoid arthritis, and certain types of blindness in elderly patients (age-related macular degeneration) and in patients with diabetes (diabetic retinopathy).




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