Drug therapies that harness the immune system’s natural ability to fight cancer have been advancing at a fast pace since the first immunotherapy drug was approved in 2011. These early immunotherapy drugs—called checkpoint inhibitors—work by triggering the immune system to attack cancer cells. But a new and highly personalized type of immunotherapy drug uses a patient’s synthetically modified T cells—a type of white blood cell—to kill cancer cells. This is called chimeric antigen receptor (CAR) T-cell therapy.
Think of your T cells as police officers on a beat. They patrol the body’s bloodstream in search of foreign invaders, from harmful bacteria to cancer cells. They have specialized receptors that recognize these unwanted intruders by detecting certain proteins on their surfaces. In CAR T-cell therapy, synthetically engineered receptors designed to detect the cancer cell’s protein are attached to a sample of a patient’s T cells taken from a blood draw. Then, in a laboratory, hundreds of millions of these modified T cells are grown before the cells are re-infused back into the patient. If the therapy is successful, these cells begin recognizing and killing cancer cells.
"CAR T is an exciting new form of immunotherapy that is proving effective in patients with certain recurrent or resistant blood cancers,” says Yale Medicine hematologist Stuart Seropian, MD, who is co-director of the CAR T-Cell Therapy program at Yale New Haven Health’s Smilow Cancer Hospital, the first hospital in Connecticut to perform the therapy.
At Yale Medicine, CAR T-cell therapy offers highly personalized therapy options for patients with certain types of blood cancers such as relapsed or refractory B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. “This therapy could help patients who have already tried chemotherapy, or who do not have alternative treatment options,” says Yale Medicine pediatric hematologist oncologist Niketa Shah, MD.
Which cancers can CAR T-cell therapy treat now?
The Food and Drug Administration (FDA) has approved two types of CAR T-cell therapy drugs. Tisagenlecleucel (brand name Kymriah) works on patients up to age 25 with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Axicabtagene ciloleucel (Yescarta) treats adults ages 18 and older with large B-cell lymphoma. Scientists are working to develop other types of CAR T-cell therapies for a range of different cancers.
Not many hospitals or cancer centers are able to offer CAR T-cell therapy at present, as the drugs can only be made in highly specialized laboratories that have gone through a rigorous certification process that allows them to produce the drugs onsite. Smilow Cancer Hospital, where Yale Medicine physicians practice, is the first in Connecticut to offer CAR T-cell therapy.
What are possible side effects of CAR T-cell therapy?
All cancer treatments come with a risk of side effects. However, there are some specific to CAR T-cell therapy:
- Cytokine release syndrome (CRS). This is one of the more frequent side effects of CAR T-cell therapy. Cytokines are chemical messengers released by the T cells to help direct actions of the immune system. CRS arises when too many cytokines are produced by the engineered T cells, leading to extremely high fevers or a severe drop in blood pressure. On the other hand, physicians interpret CRS as a sign that the infused T cells are working in the body. Some CRS symptoms can be managed with steroids and a drug called tocilizumab, another anti-inflammatory drug.
- Brain swelling and inflammation. Reported in a few patients, this can be a very dangerous side effect if not addressed quickly.
- Dying B-cells. A type of white blood cell, B cells are part of the adaptive part of the immune system that reacts to specific infections. B cells produce antibodies, which are proteins in the blood that remember previous infections and provide protection against them. Occasionally, the engineered receptor on the T cells can also target healthy B cells, and this can lead to dangerously low levels of immunoglobulin, the part of the blood plasma that contains all of these antibodies, putting the person at a significant risk of an infection.
What is next for CAR T-cell therapy?
Researchers are testing ways to produce modified T cells without having to harvest them from the patient. This type of medicine is called “off-the-shelf,” a nod to its ability to be used immediately, without any modification in a laboratory, just like regular chemotherapy or the aspirin you buy at a drug store.
How is Yale Medicine unique in its approach to CAR T-cell therapy?
“Yale has a unique platform to provide this advanced immunotherapy treatment due to a well-trained team of physicians, nurses, and laboratory personnel who can handle complex care plans required of for CAR T-cell therapy,” Dr. Shah says.