Cancer cells have a variety of ways of evading detection by the immune system. CAR T cell therapy, which is sometimes described as adoptive cell transfer (ACT), is aimed at enhancing T cells, the “attack” arm of the immune system, so that they do a better job of recognizing and destroying cancer cells. (1) CAR T cell therapy has shown encouraging results in two uses approved by the Food and Drug Administration (FDA). In August 2017 the FDA approved Kymriah (tisagenlecleucel) for some children and adults with advanced B cell leukemias. In October, 2017, the FDA approved the second CAR T cell therapy. The second approval was for the use of Yescarta (axicabtagene ciloleucel) for use in certain patients with B-cell lymphomas. For a long time, this kind of personalized therapy remained little more than a researcher’s dream. The technology was exceedingly complex, and the initial success was just enough to encourage a handful of researchers to continue the work. Only now is the research at a stage at which it is being approved by the FDA and can begin helping patients.
Amping Up the Immune System’s Ability to Find and Kill Invaders
The immune system functions as both a sentry, scanning the body for invaders such as bacteria and viruses, and an attack force, destroying those invaders if they should appear. It consists of antibodies, a type of protein that can attach to invading bacteria and viruses and kill them; and living cells, such as T cells, a type of white blood cell capable of recognizing and killing cells in your body that are not “normal” — whether they be infected with a virus or bacteria or if they are cancer cells that look “foreign” compared with your normal cells. (2) Using CAR T cells in cancer therapy involves collecting patients’ own immune cells. To do this, blood is drawn from patients and T cells are extracted. In CAR T cell therapy, the T cells are engineered to produce receptors — biologic keys of sorts — on their surface called chimeric antigen receptors, or CARs. These receptors are constructed to latch on to specific proteins on the surface of tumor cells. (2) Certain forms of leukemia or lymphoma, for example, have a protein on their surface called CD19. CAR T cell treatments engineered to connect to the CD19 protein will latch on to cancers that carry that protein. The T cell then proceeds to kill the cancer cell. (2)
How CAR T Cells Are Made: From the Bloodstream to the Lab and Back to the Patient
Making CAR T cells can take several weeks. Doctors begin by removing T cells from the patient’s bloodstream. In this procedure, the patient reclines in a chair for two to three hours while he or she is attached to two intravenous (IV) lines. Blood is drawn out through one line, T cells are removed from the blood, and then blood is routed back into the patient through the other IV line. (3) The T cells are then sent to a laboratory where the appropriate CAR is added to the T cell, making them CAR T cells specifically targeted to the patient’s tumor. These are infused back in to the patient through an IV. When they start binding with cancer cells, they increase in number and can move on to attack more cancer cells. (3)
CAR T Cell Therapy Is Not Without Side Effects
Some patients experience very high fevers when given CAR T cells, or dangerously low blood pressure in the days after the treatment is administered. This is caused by cytokine release syndrome. Cytokines are small proteins produced by immune cells that help cells communicate with one another. In cytokine release syndrome, cells affected by the CAR T cell therapy release a large quantity of cytokines into the bloodstream. Oncologists are developing ways to manage this side effect. Some patients may develop serious infections or a weakened immune system, as well as neurological symptoms that include confusion, seizures, and severe headaches. Patients should be aware of these symptoms so that they can notify their doctors immediately if they develop any of them. (3)
Difficulties With Widespread Use of CAR T Cells
Adoptive cellular immunotherapies have been available for some 20 years, but it has been difficult to make them predictable and practical. Many have to be made from the patient’s own cells, which is like producing a personal cancer therapy for each patient. Every such therapy is, in effect, an orphan drug that cannot be manufactured easily and inexpensively for millions or patients, according to a review published in January 2014 in the journal Immunological Reviews. So far, CAR-T cell therapy has been approved for two uses, as mentioned above. One is recurrent acute B cell lymphoblastic leukemia in children and young adults. The other is for certain forms of advanced or recurrent B-cell lymphoma (one of several types of non-Hodgkin’s lymphoma). It is unclear at this stage how well these therapies will work for solid tumors, such as breast and colorectal cancer. Different forms of adoptive cell transfer are being developed for other forms of cancer. (1)
Are CAR T Cell Treatments a Cure for Cancer?
These treatments have shown encouraging results in use against acute lymphoblastic leukemia and recurrent large B-cell lymphoma. In many patient cases, cancer could not be found after treatment. But this therapy is so new that patients have not been followed for a long time after treatment and it’s not known yet whether these are long-term cures. In some patients, the CAR T cells disappear after the cancer has been in remission, and it’s unclear whether the cancer could come back in the absence of the CAR T cells. CAR T cell therapies are now being tested for use against brain tumors (especially glioblastoma), breast cancer, Hodgkin’s lymphoma, neuroblastoma, pancreatic cancer, and others. (1)
