Potential carbohydate-based vaccines against breast cancer
January 29, 2013 § Leave a comment
In a paper just out in Proceedings of the National Academy of Sciences, researchers describe the development of carbohydrate-based vaccines against breast cancer. One of the vaccines is in clinical trials for terminal-stage breast cancer patients.
Chi-Huey Wong at the Academia Sinica in Taiwan says he and his colleagues have been searching for unique cancer biomarkers as targets for vaccine development. Unfortunately, most cancer-related proteins are either upregulated or downregulated instead of being uniquely expressed. These proteins are not good candidates for vaccine design “as the antibodies generated from immunization may also attack normal cells and thus cause autoimmune disease,” explains Wong.
Instead, the investigators decided to look at sugars attached to either proteins or lipids that were expressed on the surface of cancer cells. By using enzymatic methods and mass spectrometry, they were able to identify a number of unusual sugar structures on the cell surfaces of several types of cancers, including breast cancer and breast cancer stem cells.
The investigators decided to design vaccines that would induce antibodies, in particular IgG, to target three unique sugar structures called SSEA4, GloboH and Gb5. But they had to proceed with caution. “We know carbohydrates are not good immunogens and often induce IgM antibodies, which are less desirable,” says Wong.
But he and his colleagues found that they could develop carbohydrate-based vaccines that targeted these markers. When they carefully chose the vaccine carrier proteins, adjuvant and other molecules, they were able to coax the immune system to generate more IgG than IgM antibodies.
One of the vaccines Wong and colleagues developed, called GloboH-KLH/QS21, is now undergoing phase II and III clinical trials in terminal-stage breast cancer patients. The investigators also are focusing on another vaccine, SSEA4-DT/C34, which is more selective for SSEA4, GloboH and Gb5 and generates more IgGs than the GloboH-KLH/QS21 vaccine. The SSEA4-DT/C34 vaccine is targeted against breast cancer but also may have applications in pancreatic, ovarian and lung cancers, says Wong.