Much-sought-after cancer vaccine on the anvilNovember 14th, 2007 - 3:03 am ICT by admin
“In mice we can illicit very strong antibody responses and we have shown that the antibody responses are functional - that they can kill cancer cells,” Nature quoted lead author Geert-Jan Boons, Franklin professor of chemistry, as saying.
At present, vaccines are used to thwart diseases by priming the immune system to identify and attack a virus or bacteria. However, the vaccine that Boons and his team have synthesized is a therapeutic vaccine that trains the body’s immune system to fight an existing disease.
The discovery in the 1970s of unique sugars on cancer cells set scientists in search of a way to get the immune system to distinguish and attack cells that express these cancer-associated sugars. So far, however, the results have been less than impressive.
According to Boons, early cancer vaccines were created by linking the tumor-associated carbohydrate with a foreign protein. The immune system, perhaps not surprisingly, attacked the protein and the linker molecules, but generally left the carbohydrate alone.
“We needed to come up with a vaccine that does not give our immune system a chance to go after anything else but the tumor-associated carbohydrate. In other words, there should no junk that can induce an immune response to something other than the tumor-associated carbohydrate,” Boons said.
Boons and his team developed a vaccine synthetically from scratch by piling molecules together and arranging them in the appropriate configuration. In 2005, they created a fully synthetic vaccine that stimulated an immune response to the tumour-associated carbohydrate alone. The vaccine stimulated only low antibody levels, however, so the researchers began optimising the components of the vaccine to illicit a stronger immune response.
Their optimised vaccine includes a tumour-associated carbohydrate that triggers the immune system’s B cells, a part of a protein that triggers the immune system’s T cells and a linker molecule that stimulates the production of generalized immune components known as cytokines.
The results of their three-pronged approach were surprising, principally with regard to a critical component of the immune system known as IgG.
“When we tested our best vaccine we got really, really fabulous antibody levels that have never been seen before. The levels of IgG antibody production were 100 times better than with conventional approaches,” Boons said.
He added that the vaccine has been effective in creating an antibody response that can kill cultured epithelial cells, those commonly involved in most solid tumours, such as breast and colorectal cancer, derived from mice and in stimulating an immune response in healthy mice.
The researchers are presently testing the vaccine in mice with cancer, and Boons hopes to start phase I clinical trials in humans within a year.
However, despite his zeal for his work, Boons warns that it’s too early to predict how the vaccine will perform in humans.
“There’s a very big step going from mice to humans. Other cancer vaccines have worked in mice but not in humans,” he said.
The finding is published in the October issue of the journal Nature Chemical Biology. (ANI)
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