June 26, 2008 Mice immunized with an intestinal protein developed fewer lung and liver metastases following injection with colon cancer cells than unvaccinated animals, according to a study in the June 24 issue of the Journal of the National Cancer Institute.
Researchers are hindered in the development of cancer vaccines by a lack of antigens that are specific for tumors and not expressed elsewhere in the body. Immunization with antigens that are expressed elsewhere in the body raises the possibility of autoimmune complications. However, the intestinal lining and some other mucosal areas are protected from the immune system and some proteins from these immune protected sites are widely expressed on tumor cells. Therefore such proteins may be safe and effective antigens for anti-cancer vaccines.
To test this possibility, Adam Snook, Ph.D., and Scott Waldman, M.D., Ph.D., of Thomas Jefferson University in Philadelphia and colleagues immunized mice with a viral vector that expressed guanylyl cyclase C protein, which is normally only expressed in the intestinal lining and is expressed by metastatic colorectal cancer cells. The researchers injected the animals with colon cancer cells before or after immunization with guanylyl cyclase C.
The vaccinated animals developed fewer metastases in the liver and lung compared with control animals. Vaccination also prolonged overall survival, with a median of 38 days in immunized animals and 29 days in control animals. The investigators did not see any evidence of autoimmune responses.
The researchers hypothesize that the approach of using antigens from immune-restricted sites might be extended to other cancers that originate from mucosa, including cancers of the head and neck, lung, breast, vagina, and bladder.
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- Snook et al. Guanylyl Cyclase C-Induced Immunotherapeutic Responses Opposing Tumor Metastases Without Autoimmunity. JNCI Journal of the National Cancer Institute, 2008; DOI: 10.1093/jnci/djn178
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