Reporting online Tuesday, June 24, 2008 in the Journal of the National Cancer Institute, Scott Waldman, M.D., Ph.D., professor and chair of Pharmacology and Experimental Therapeutics at Jefferson Medical College of Thomas Jefferson University and his co-workers have shown that mice immunized with an intestinal protein developed fewer lung and liver metastases after injection with colon cancer cells than did control animals that were not immunized. The work may portend the development of a different kind of cancer vaccine, the researchers say, that may help prevent disease recurrence.
One of the reasons that cancer vaccines have been disappointing in many cases is the lack of immune system-alerting protein antigens that are specific for tumors only. According to Dr. Waldman, mucosal cells, which line the intestines (colon cancer arises from mucosal cells, and mucosal cell proteins continue to be expressed even after they become cancer) are essentially compartmentalized and possess a separate and distinct immune system from the body's general immune system. He and his group thought that such proteins would be seen as foreign by the latter system and be useful for anti-cancer vaccines.
Dr. Waldman, postdoctoral fellow Adam Snook, Ph.D., and their colleagues engineered viruses – 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 researchers injected the animals with colon cancer cells before or after immunization.
They found that the vaccinated animals developed fewer metastases in the liver and lung – 90 percent and 75 percent, respectively – compared with control animals. Vaccination also prolonged overall survival, with a median of 38 days in immunized animals and 29 days in control animals.
"We think this identifies a novel class of vaccine candidate targets for tumors that originate and metastasize from mucosa, like colorectal cancer," Dr. Waldman says. "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."
Dr. Waldman sees GCC as "the poster child" for mucosal antigens. "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," he explains. "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 says, 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."
"This paper demonstrates the profile of a model cancer mucosal antigen class that can generate systemic immune responses," he says. "There is incomplete systemic tolerance to these antigens, as we predicted, and that the immune responses have anti-tumor efficacy and the animals are free of autoimmune 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. Adding mucosal antigens from the same tumor type might also enable the development of a "polyvalent" vaccine, Dr. Waldman notes.
Steve Benowitz | EurekAlert!
Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
16.11.2018 | Health and Medicine
16.11.2018 | Life Sciences
16.11.2018 | Life Sciences