The science of immunotherapy,
Manipulating the immune system to fight disease has been the longstanding goal of medical science.
Then, in 2010, Carl H. June and his University of Pennsylvania School of Medicine research team engineered immune cells to successfully treat two patients with chronic lymphocytic leukemia who achieved full remission with partial remission for a third patient. The world took notice and cheered. And that success helped to further inspire immunotherapy research worldwide.
It makes good sense. The immune system is our natural method of healing. So bolster the immune system — the T cells — to treat cancer. Desensitize them to treat autoimmune diseases. Prevent them from rejecting transplanted organs. Make better vaccines to more universally fight viral and bacterial infections.
Then there’s inflammation — chronic over-activation of the immune system that adversely affects health on multiple fronts and apparently is a factor in aging.
All of this explains the forces that led to creation of the UPMC Immune Transplant and Therapy Center in Bloomfield to develop treatments useful to fight cancer, autoimmune disease, transplant rejection and aging.
Typically, academic research centers hand off their drugs to pharmaceutical companies to test, get approval and market. But the center will perform clinical trials then go through the expensive and often lengthy approval process by the U.S. Food and Drug Administration before marketing and distributing new drug products worldwide.
UPMC officials call the vertical concept as “bench to bedside” — drug development to marketplace.
“It turns out that the immune system has an impact on so many aspects of human health, and more than we originally thought,” said Mark Shlomchik, a UPMC endowed professor of immunology and chair of the Pitt School of Medicine’s Department of Immunology. “Many people understand the immune system fighting viral or bacterial infections, explaining our natural ability to kill germs. People also are aware of how vaccines work by using noninfectious forms [of the virus or bacteria] to teach the immune system, which has a memory. Then when an infection comes along, it can resist it.”
But with autoimmune diseases, he said, the immune system is overzealous and starts attacking healthy cells and tissue, be they insulinproducing beta cells, joint tissue in rheumatoid arthritis or the myelin sheath around nerve cells in multiple sclerosis, among many others. Also, in protecting transplanted organs, the key is preventing the immune system permanently from attacking the donor organ.
“Sometimes when the immune system is too charged up, you want to put the brakes on,” Dr. Shlomchik said.
Then there’s cancer, where the tumor has many ways of winning the battle against the immune system, either by growing faster than T cells can react, or hiding fromor deactivating them.
“In the last several years, there have been some breakthroughs where we’ve learned to give the advantage back to the immune system, and take the brakes off, and now there are several drugs approved by the FDA to treat melanoma, lung and kidney cancers,” he said. “This is like Jimmy Carter’s [melanoma that spread to his liver and brain]. He was put on a drug and the tumor naturally regressed. It involves taking the brakes off the immune system, and the immune system naturally destroys the tumor.”
These drugs known as checkpoint inhibitors prevent degradation of immune cells at certain steps during the immune response. For now, however, the drugs work only 20 percent to 40 percent of the time, which means success to many patients but leaves many others without alternative treatments.
“Various researchers at Pitt are trying to turn T cells back on. We capture T cells in a tumor that are doing their job but not winning the battle,” Dr. Shlomchik said. “They are regenerated [in a laboratory] up to a thousandfold and re-energized.” Then they are reintroduced.
“From a small band of soldiers, we are making an army that can kill the tumor,” he said.
A fluorescence-colored microscope image from the National Institutes of Health shows a culture of human breast cancer cells.