Key words :
cancer,
therapy
,tumor
,immune system
,b cells
,cytokines
,t cells
,vacciné
,antibody
,carbohydrate
,cancer
A Vaccine for Cancer
12 Nov, 2007 10:21 am
Efforts to train the immune system to attack cancer cells has been met with limited success, mainly because the immune system recognizes cancer cells as self. Our team at the University of Georgia has created a fully synthetic carbohydrate-based vaccine that has successfully triggered a strong immune response to cancer cells in mice.
Current vaccines are preventive and work by priming the immune system to attack foreign invaders such as viruses and bacteria. Our investigational vaccine, on the other hand, is therapeutic and works by training the immune system to recognize and attack cells bearing sugars on their surfaces that are unique to cancer.
Early cancer vaccines were created by linking the tumor-associated carbohydrate with a foreign protein. These vaccines elicited a response to the protein and linker molecules, but, at best, generated a weak response to the carbohydrate.
To overcome these limitations, our team constructed a fully synthetic vaccine with the goal of inducing an immune response to the tumor-associated carbohydrate alone. In 2005, we reported our results and showed that our vaccine stimulated an immune response to the tumor-associated carbohydrate alone. The vaccine stimulated only low antibody levels, however, so we began optimizing the components of the vaccine to elicit a stronger immune response.
Our optimized vaccine includes a tumor-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.
Our three-pronged approach has yielded remarkable results, particularly with respect to a critical component of the immune system known as IgG.
Our levels of IgG antibody production were 100 times better than with conventional approaches. Levels this high have not been reported in the scientific literature before.
The vaccine has been successful in creating an antibody response that can kill cultured mouse epithelial cells, which are commonly involved in most solid tumors, such as breast and colorectal cancer. The vaccine has also been shown to stimulate an immune response in healthy mice. We are currently testing the vaccine in mice with cancer, and hope to start phase I clinical trials in humans within a year.
A major caveat is worth noting: It’s too early to predict how the vaccine will perform in humans. Other cancer vaccines have been successful in mice but not humans. Still, we are enthusiastic about our finding and its demonstration of the benefits of creating fully synthetic vaccines.
In addition to testing the new vaccine, we are exploring the specific components of the immune response as they relate to cancer, determining the exact cytokines and antibodies that are most effective against cancer cells. Understanding which molecules are being upregulated at each level of the immune response gives us a road map to further optimize each component of the vaccine.
References:
1. Ingale, S., Wolfert, M., Gaekwad, J. & Boons, G.J. Robust immune responses elicited by a fully synthetic three-component vaccine. Nature Chemical Biology 3, 663-667 (2007).
2. Buskas, T., Ingale, S. & Boons, G.J. Towards a fully synthetic carbohydrate based anticancer vaccine: synthesis and immunological evaluation of a lipidated glycopeptide containing the tumor-associated Tn antigen. Angew. Chem. Int. Ed. 44, 5985–5988 (2005).
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