Animals immunized with an intestinal protein developed fewer lung and liver metastases after injection with colon cancer cells, according to paper in the Journal of the National Cancer Institute.



Scientists at the Kimmel Cancer Center at Jefferson Medical College have found a way to immunize mice against the development of metastatic disease. Their approach is based on the fact that the intestines have a separate immune system from the rest of the body. The researchers were able to show that mice immunized with an intestinal protein developed fewer lung and liver metastases after injection with colon cancer cells than did control animals.


Mucosal cells line the intestines, which are compartmentalized and possess a separate immune system from the body’s general immune system. Colon cancer arises from mucosal cells, and mucosal cell proteins continue to be expressed even after the cancer sets in. The research team thus hypothesized that these proteins would be seen as foreign invaders by the body’s immune system and could be useful for anticancer vaccines.


They engineered adenovirus, vaccinia, and rabies to express the protein guanylyl cyclase C (GCC), which is normally found in the intestinal lining and in metastatic colon cancer. The scientists injected the animals with colon cancer cells before or after immunizing with GCC.


They found that the vaccinated animals developed 90% fewer metastases in the liver and 70% fewer in the lungs. Vaccination also prolonged overall survival, with a median of 38 days in immunized animals and 29 days in control animals, the investigators report.


“Immunizing an animal or person systemically with GCC will be recognized to some degree as foreign, and the body will mount an immune response in the systemic compartment,” according to Scott Waldman, M.D., Ph.D., professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College. “We think that the immune response will be effective against the cancer, but it won’t cross over into the intestines and cause autoimmune disease.”


As a result, he adds, the immune responses against GCC could be used both prophylactically and therapeutically. “The target populations for such a vaccine are patients who have had surgery and adjuvant chemotherapy and have no evidence of disease. If they have recurrence, it’s from microscopic disease.”


The researchers suggest that this approach of using antigens from tumors originating in immune-restricted sites might be extended to other cancers that originate from mucosal cells, including cancers of the head and neck, lung, breast, vagina, and bladder.


The results of the study appear online on June 24 in the Journal of the National Cancer Institute.








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