Chemists at the Sloan-Kettering Institute for Cancer Research have created a novel vaccine they hope will thwart prostate cancer. Now in early human trials, the vaccine is the first made synthetically to target abundant, but elusive, carbohydrates on the surface of tumor cells.
The development will be outlined in the November 20 Web edition of the Journal of the American Chemical Society, published by the American Chemical Society, the world's largest scientific society. It is scheduled to appear in the print version of the peer-reviewed journal on November 25.
Using vaccines to stimulate an immune response against cancer typically focuses on proteins, which are relatively easy to make but often arelodged within cells and not easily accessible to antibodies. Most of the good targets, or antigens, on a cancer cell's surface are not proteins, however. Instead they are small, difficult to synthesize carbohydrates whose immunogenicity is not well-understood.
"Normally the carbohydrates are much more complex in normal cells. In cancer cells they're often very different," says lead author and Sloan Kettering Institute for Cancer Research chemist Scott D. Kuduk, Ph.D. The difference should enable scientists to exclusively target cancer.
Kuduk, who works in the lab of Kettering Chair and Director of Bioorganic Chemistry, Samuel J. Danishefsky, Ph.D., says their group successfully synthesized two key tumor carbohydrate antigens -- called TF and Tn. They then clustered the antigens as they occur naturally and attached them to proteins which help produce an immune response. "Through chemistry, we were able to make substantial quantities of the material that allowed us to then do the testing," adds Kuduk. In mice, the Tn-protein complex was especially effective at triggering antibody production.
"It's a wonderful antigen for prostate cancer because Tn is one of the main antigens on prostate cancer cells," according to co-author and Sloan Kettering Immunologist Philip O. Livingston, M.D., who calls the advance "more promising than other approaches."
The new vaccine is being given to patients who have undergone prostate cancer surgery, hoping to ward off a recurrence. Though it is too early to know whether a series of vaccinations will provide an adequate defense, Livingston says patients are definitely producing antibodies against Tn. Scientists hope the vaccines will specifically attack prostate cancer cells, thereby permanently curbing cancer and reducing the side effects usually associated with chemotherapy.
A nonprofit organization with a membership of more than 155,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.
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