Cancer Immunotherapy 101
Let's start with the bottom line: the human immune system is capable of identifying, targeting and killing cancer cells. In fact, at some point in almost everyone's life, they will have a few cancerous cells that are destroyed by the immune system before they ever become the disease we think of as cancer.
When those cancerous cells turn into the disease, they have escaped from the immune system's control as it currently exists. To do so, cancer cells have developed a number of ways to evade the immune system and tip the scales in favor of their harmful growth.
In cancer immunotherapy, the goal of treatment is to boost the cancer-killing capabilities that the immune system already has, tipping the scales back in favor of the immune system. Since 1968, when University of Wisconsin physician-researcher Dr. Fritz Bach determined how to match donors and then led the UW team that performed one of the world's first two bone marrow transplants, UW has established itself as a leader in immunotherapy approaches to life-threatening childhood diseases - a distinction our Pediatric Cancer Dream Team continues to this day.
The Immune System
The immune system is the body's defense system, protecting us against infectious invaders like bacteria and viruses. When one of our own cells is under attack, it "shows" little pieces of the invader on its surface, signaling to the immune system that something is not right inside that cell.
Cancer works the same way: a cancerous cell is "showing" mutated or modified proteins, again signaling to the immune system that there is a problem inside that cell.
The immune system is a complex system of cells and tissues and fluids that all work to rid the body of these problems. All cells of the immune system start as stem cells in the bone marrow, then they develop into different immune cells and travel through the blood or lymphatic system.
You'll hear lots of different immune cell names - T cells, B cells, natural killer cells, dendritic cells, bone marrow stem cells - and names of chemicals those cells secrete, called cytokines. The details of what they all do is not as important for now, but you may wish to at least know some of these terms.
Cancer Cell Evasion and Escape
If the immune system is capable of recognizing and fighting cancer cells, why do we ever develop cancer? Unfortunately, cancer cells have found ways to survive, even with the immune system around.
- Cancer cells are "self" cells: Your immune cells are trained to recognize the difference between a healthy self cell and an unsafe foreign cell. The problem with cancer is that it is both a healthy self cell AND an unsafe cell. Cancer cells take advantage of this feature, and can trick the immune system into ignoring the unhealthy part and only recognizing the "self" part.
- Cancer cells are immunosuppressive: Cytokines are the immune system's chemical way of communicating. In some cases, cells use cytokines to signal that they are diseased and need the immune system to help. In other cases, the cytokine signal actually weakens the immune response to the cell. Cancer cells frequently send the cytokine signal that weaken the immune response.
Fighting Back: Immunotherapies
We know the immune system has the potential to recognize and kill cancer cells, it just might need a little boost. Cancer immunotherapies are one of the most promising areas of research right now. There are a few different types of immunotherapy, and in many cases they are combined to become even more effective:
Traditional Chemotherapy and Radiation
By targeting cancer cells with these traditional therapies, the immune system is boosted in several ways:
- The number of cancer cells to fight is decreased.
- The death of the cells releases cancerous proteins for the immune system to recognize.
- Fewer cells mean less immunosuppressive cytokines. While effective, these traditional therapies are often non-specific and very physically and emotionally demanding on patients. At UW, our researchers are finding ways to use the non-traditional treatments, below, to reduce side effects and cure more kids of cancer.
All vaccines work by training or boosting the immune system to recognize antigens, or small fragments of foreign proteins or other pieces that the immune cells can recognize with high specificity. Unlike most vaccines, which typically prevent disease, cancer vaccines are given after a patient has developed cancer to boost their immune cells' ability to recognize a specific cancer antigen. Most vaccine research is currently being done for adult cancers, but childhood cancer vaccines are also being investigated.
Adoptive T-cell Therapies
T-cells are a type of immune cell that can kill cancer cells, if they recognize the cell as cancerous and can bind to the cancer antigen. In this type of therapy, either T-cells that can already recognize a patient's cancer antigens are isolated and grown in the lab, or they are genetically engineered to recognize cancer antigens. Then the cancer-fighting T-cells are put back into a patient to fight the cancer.
The University of Wisconsin is pioneering clinical trials in these areas:
- Dr. Christian Capitini is leading UW's effort in a collaborative national study that is testing the ability of genetically modified T-cells to act directly against childhood leukemia.
- Dr. Mario Otto is leading a trial, open only at UW, that is using a new form of bone marrow transplant cell preparation to enhance the T-cell attack on residual leukemia or solid tumors.
Antibodies are just free-floating antigen finders. They are made and then released by B cells. They can work in one of a few ways:
- They can bind to cancer antigens and act as a signal to natural killer cells to kill the cell.
- They can block a protein on the cancer cell's surface that it needs to survive.
- They can deliver cancer-fighting drugs directly to the cancer cells and only the cancer cells.
Research under way in this area include the following:
- Dr. Paul Sondel and his research team have been pursuing this approach in the fight against neuroblastoma for more than 25 years, leading to a treatment that was recently approved by the U.S. Food and Drug Administration (FDA) as part of the standard of care for all children with high-risk neuroblastoma. In December 2016, the Society for Immunotherapy of Cancer (SITC) announced that Sondel, a pediatric oncologist, had received the group's top award for decades of work in developing immunotherapies for childhood cancers, especially neuroblastoma.
- Dr. Ken DeSantes is leading a novel clinical trial that combines this approach with adoptive cell therapy for children with neuroblastoma whose disease has failed to respond to standard therapies.
The Future of Immunotherapy
Every cancer is unique and complex, and every person's immune system responds a little differently. While we have come a long way in understanding the immune system and how to use it to tackle cancer, there is still much to be learned.
At the University of Wisconsin Carbone Cancer Center and American Family Children's Hospital, there are several active laboratory and clinical research projects happening right now (yes, even as you read this, someone is doing research!).