Cancer researchers and other medical scientists call immunotherapy one of the most promising advances in recent decades—if not the entire history of medicine.
On the surface, it sounds simple: Immunotherapy retrains the immune system to identify and hunt down cancer and other disease cells. In the lab and in the clinic, it’s a highly advanced technology that’s changing lives.
Normally, the immune system can determine healthy cells from sick cells. But when cancer cells multiply, the immune system can’t always keep up. The immune cells become exhausted and can no longer kill mutated cells.
Immunotherapy is a treatment strategy that reprograms the immune system to fight back. T-cells—a type of immune cell—are extracted from the patient and modified in the laboratory to recognize specific markers on cancerous cells. The key ingredient is called a chimeric antigen receptor (CAR), which creates new cancer-seeking CAR T-cells.
During treatment, thousands of these supercharged CAR T-cells are infused back into the patient’s bloodstream, acting as a living drug that hunts down and kills cancer cells.
Immunotherapy can even be effective in patients who have already undergone extensive treatments for stubborn and recurring cancers. Unlike other therapies, CAR T-cells can survive in the body for years, constantly patrolling for new cancer cells and wiping them out as they appear.
A few years ago, I did not think this was possible. Now, with the promise of immunotherapy, I know we are on the right path.
Huda Salman, MD, PhD – Executive Director, Brown Center for Immunology
Currently, CAR T-cell therapy is approved by the FDA for:
Clinical trials and FDA-approved treatments have proven CAR T-cell therapy is safe and effective. The results show that the enhanced T-cells can remain in the body long enough to eliminate cancer cells – and possibly prevent them from recurring.
Patients are usually admitted to the hospital for two to three weeks. After the CAR T-cells are infused, close monitoring from the care team ensures accurate testing of the immune system’s progress, as well as a quick response to any side effects that may occur.
The most common side effect of CAR T-cell therapy is called cytokine release syndrome, or CRS. It’s also known as a “cytokine storm.” It’s a consequence of CAR T-cells multiplying in the body, and about 70 percent to 90 percent of patients experience it.
CRS starts around the second or third day after the infusion, and symptoms are usually short-lived and reversible. It’s like having a severe case of the flu, with high fever, fatigue, and body aches. If CRS is severe and lasts longer than it should, the care team can administer an FDA-approved drug called Tocilizumab.
The other side effect is known as CRES, which stands for CAR T-cell-related encephalopathy syndrome. It typically starts around day five after the infusion. Patients can become confused and disoriented, and sometimes may not be able to speak at all for a few days. CRES can be upsetting for patients and their families, but it typically is completely reversible.
The immune system uses proteins inside T-cells as a built-in mechanism to trigger appropriate responses, known as checkpoints. During an infection, T-cells fight off the infection and then turn off the response through these checkpoints. When a normal T-cell encounters a cancer cell, the combination of proteins signals the immune system to slow down or even stop the fight against the cancerous cells.
Inhibiting these checkpoint signals can release the brakes that the cancer has imposed on the immune system – and unleash powerful responses toward tumor cells to stop their progression.
CAR T-cell infusion is among a wider array of treatments known as adoptive cell therapies. Research in this area focuses on isolating immune cells and expanding their numbers to bolster the body’s cancer-fighting arsenal.
Cellular immunotherapies deploy this natural ability in several additional ways:
Monoclonal antibodies are immune system proteins created in a laboratory to bind to targets on cancerous cells. This allows the immune system to “see” the cancer as harmful to the body and attack the abnormal cells.
Treatment vaccines stimulate the body’s immune system to produce antibodies against specific antigens on a cancer cell. Treatment vaccines do not prevent cancer like other vaccines prevent disease; they are given to people who already have cancer to help their immune system have a better response.
Immune system modulators stimulate or suppress the immune system to help the body fight cancer. Some immune system modulators (such as monoclonal antibodies and cancer vaccines) affect specific parts of the immune system, however, nonspecific modulators that affect the immune system in a general way can also be used to attack cancer cells.
Donor support is crucial to advancing discoveries that will have the most meaningful impact on life-changing immunotherapies.
