February 2, 2009

Biomatrix Polymers Show Promise for Cancer Vaccines

Photo of electron micrograph showing a sponge-like porous material A close-up view of the biomatrix polymer used for the cancer vaccine.Dr. David J. Mooney, Harvard University

Researchers have developed a new kind of cancer vaccine using biomatrix polymers. When tested in mice with melanoma cancer, the vaccine yielded up to a 90% survival rate.

Vaccines are traditionally designed to prevent diseases caused by viruses and bacteria. Currently, the U.S. Food and Drug Administration has approved 2 cancer vaccines. One, against the human papilloma virus, lowers the risk of cervical, vaginal and vulvar cancer in women. The other, against the hepatitis B virus, helps prevent liver cancer. Most cancers, however, aren’t linked to an infection. Researchers are now working to develop therapeutic cancer vaccines to target pre-existing cancers.

Scientists have been investigating different strategies to direct the immune system to recognize and destroy cancer cells. One has been to inject antigens—molecules that prompt the immune system to attack—from tumor cells. Another involves manipulating dendritic cells, which present antigens to other immune system cells in lymph nodes to stimulate an attack.

A team led by Dr. David J. Mooney at Harvard University tried an innovative approach: to create a synthetic antigen-presenting structure that could attract and activate dendritic cells within the body. They used a biomatrix polymer made of poly[lactide-co-glycolide] (PLGA) a biodegradable material that has undergone significant clinical testing and received high safety ratings. Their work, funded by NIH’s National Institute of Dental and Craniofacial Research (NIDCR), appeared in the online edition of Nature Materials on January 11, 2009.

The scientists first designed the biomatrix polymer to release tumor antigens and inflammatory cytokines. Inflammatory cytokines are normally released by immune cells in the body to recruit dendritic cells to a site of infection, where they pick up antigens. The dendritic cells then migrate to lymph nodes, where they present the antigens to other immune system cells.

After developing a biomatrix polymer that could successfully attract dendritic cells in the lab, the researchers tested it by implanting it under the skin of mice with melanoma cancer. They found an increased number of dendritic cells within the polymers. More importantly, tumor formation was delayed by 40 days in half of the treated animals, and nearly a quarter of them were cured of melanoma.

The researchers next added to the mix a bacterial molecule that normally serves as a danger signal of infection to the immune system. Strikingly, the combination of the cancer antigen, inflammatory cytokine and danger signal resulted in 90% survival of mice with melanoma cancer.

PLGA and other biomatrix polymers are currently being studied for use in bone and other tissue engineering. This proof-of-principle study suggests a completely different use: reprogramming and activating immune cells to treat diseases, such as cancers, for which traditional vaccination has been disappointing.

—by Nancy Van Prooyen

Related Links