Researchers have successfully combined transgenic mouse models with a gene chip technology in a search for clues to the genes that switch the immune system on and off.
Stanford University, the Australian National University, and Eos Biotechnology in South San Francisco, California, joined forces to perform the research, which could lead to therapies for cancer, multiple sclerosis, and diabetes.
Eos expects to be testing therapies for cancer as early as next year, said David Mack, vice president of genomics research at Eos and senior author of the research, published in the 10 February issue of Nature.
The scientists said they had gotten closer to discovering what causes cells to attack invading organisms, such as viruses and bacteria, and what keeps them from attacking normal tissues.
When the immune system malfunctions, it can attack normal tissues or organs, causing an autoimmune disease such as rheumatoid arthritis. It also can cause the body to reject transplanted tissues or organs.
Currently, doctors give transplant patients immunosuppressant drugs to prevent unwanted immune responses. But the drugs cause several side effects and can't provide long-term results. Within the next several years, researchers hope they’ll be able to imitate the normal process, called "self-tolerance," which prevents cells from striking wanted tissues or organs.
Researchers used two transgenic mouse models to perform their study. One expressed a molecule as a foreign antigen, and the other model expressed the same molecule as a "self-tolerant" antigen.
"It’s an elegant mouse model that allows you to look at this biological process of tolerance," Mack said.
A special gene chip capable of displaying thousands of genes at once allowed scientists to compare the genes of each transgenic mouse model.
They compared the two models to the biological response from the drug Prograf, commonly given to organ transplant patients to suppress immune response. They found the drug response bore little resemblance to the model that tolerated the foreign molecule, which led scientists to believe that better drugs could be developed.
"The mouse model is the way it should work physiologically," Mack said. "If you really want to mimic tolerance, what you want to do is induce the profile that we defined in the mouse model."
