In the search for cancer vaccines, researchers are often foiled by the lack of antigens — proteins, usually, that generate antibodies and can cause an immune response — that are tumor-specific and not found elsewhere in the body. If a patient is immunized with antigens that the body also expresses somewhere else, autoimmune complications can result.
However, the intestinal lining's mucous membrane (or mucosa) has a different immune system from the rest of the body, and proteins from those areas may be effective antigens in anti-cancer vaccines even if they are expressed elsewhere.
To test that theory, Adam Snook and Scott Waldman of Thomas Jefferson University in Philadelphia immunized mice with a protein that is normally only expressed in the intestinal lining, and is also expressed by metastatic colon cancer cells. Their study is described online in the June 24 issue of the Journal of the National Cancer Institute.
The vaccinated mice developed 90 percent fewer metastases in the liver and 75 percent fewer in the 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.
"We think this identifies a novel class of vaccine candidate targets for tumors that originate and metastasize from mucosa, like colorectal cancer," Waldman said. "Mucosal cells turn into cancer, invade the wall of the intestine, breech the compartment and metastasize, carrying with them all the antigens that typically reside in the mucosal system. They continue to be expressed by tumors that originate in the mucosa even when those tumors metastasize into the systemic compartment where they don't belong."
The researchers are hopeful that their approach of using antigens from immune-restricted sites might be applied to other cancers that originate from mucosa, including cancers of the head and neck, lung, breast, vagina and bladder.