Research Update Corner
By Mila McCurrach
Cancer Immunotherapy- Spring 2014
Cancer Immunotherapy, the use of a person's own natural immune system to kill cancer cells, has been hailed as the 2013 breakthrough of the year by Science magazine, a leading research journal. Immunotherapy is being tested now in several types of cancer, including pancreatic cancer. Many readers want to know what exactly is this new type of therapy and how does it work?
To begin to understand immunotherapy, one has to have a basic knowledge of the immune system itself. When functioning properly, the immune system identifies and attacks a variety of threats, including viruses, bacteria, parasites and to some degree cancer, while distinguishing these foreign substances from the bodies' own healthy tissue. The immune system includes several organs that make a variety of different types of white blood cells and a complex communications system to coordinate them. For example, certain cells in the immune system constantly check every cell and tissue in the body to look for invaders that don't belong. When an invader is detected, these cells release a series of substance that raise the alarm for the immune system's soldiers, white blood cells called the B and T-cells. These cells then identify specifically who the invader is and the T-Cells tell the body to produce many more cells trained to find and kill the invader. B-cells assist in the attack by making antibodies that stick to and flag cells that should be destroyed.
Immunotherapy Strategies- Targeting the Pancreas
Several different strategies are being developed by cancer researchers to find and fight the invaders in the body and kill the cancer cells. The Lustgarten Foundation has recently focused a significant effort to develop new immunotherapy strategies to kill pancreatic cancers. Our recently announced Stand Up To Cancer-Lustgarten Foundation Dream Team includes new clinical trials to test sever new immunotherapy techniques in patients.
One of the approaches researchers are using is to stimulate the immune system to make a lot of B and T cells that specifically recognize pancreatic cancer. This cancer vaccine, used by Dr. Jaffe in her Dream Team project, is an injection of modified pancreatic cancer cells into patients that will "teach" T cells to recognize and kill the cancer cells. This vaccine approach has already shown some effectiveness in patients, but in an effort to improve it significantly, the Dream Team will combine it with different drugs that strengthen the immune system. Additionally, to make sure that the immune cells attack only foreign invaders, the immune system has a
"We believe that the immune system
ultimately has the power to
cure pancreatic cancer."
Dr. Robert Vonderheide
complex series of safety mechanisms called "checkpoints" that help it to distinguish healthy cells from infected cells. Since cancer cells are mostly normal cells that grow quickly, the immune system does not recognize them as a threat. To help the immune system build a large "fighting force" against pancreatic cancer, the Dream Team will use several drugs that relax the immune system checkpoints and make it easier to recognize and kill pancreatic cancers.
Another approach that The Lustgarten Foundation is funding is Dr. Carl June's project at the University of Pennsylvania. In a small clinical trial, Dr. June is taking blood from pancreatic cancer patients and harvesting their T cells. Using a revolutionary new approach, the T cells are then genetically modified to express protein complexes known as chimeric antigen receptors (CARs), which act as a tool to help patient's T cells recognize and destroy cancer in their body. The altered T cells are put back into the patient so his or her immune system can begin fighting the pancreatic cancer.
Immunotherapy Strategies- Removing Pancreatic Cancer Defenses
One surprising discovery that has emerged recently is that pancreatic cancer cells can actually drive white blood cells away from the tumor. This could be a problem for immunotherapies that teach white blood cells to recognize cancer cells since they have to get close to the cancer cells to recognize and kill them. Pancreatic cancers release signals that calm the immune system, which cause white blood cells to steer clear of the cancer, instead of sniffing around for invaders. Fortunately, the research scientists we are funding have discovered several drugs that can block the ability of pancreatic cancers to keep the immune system at bay. When these drugs are given to mice with pancreatic cancer and their immune system is taught what to look for, the cancer literally disappears. We are now going to test the same drug in clinical trials in pancreatic cancer patients.
While immunotherapy is still in its earliest stages, it has had some dramatic effects when used in other types of cancer like leukemia and melanoma, and we are hopeful that our experience and understanding of pancreatic cancer and the immune system, will find new therapies for our patients.