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CAR T-cell therapy uses the patient’s own immune cells to personalize cancer immunotherapy.
CAR T-cell therapy is a cancer treatment that uses a patient’s own immune system cells, called T cells, after these cells have been modified to better recognize and kill the patient’s cancer. The T cells are engineered in the laboratory and then expanded to large numbers and infused back into the patient. This type of treatment transfers an immune system into the patient that is capable of immediately killing the cancer. CAR stands for chimeric antigen receptor, which represents the genetically engineered portion of the T cell. The CAR part of the T cell contains proteins that allow the T cells to recognize the specific cancer cells as well as become highly activated to kill the cancer cells.
Once in the body, the CAR T cells can further grow to large numbers, persist for long periods of time, and provide ongoing tumor control and possible protection against recurrence.
The first step is to collect the patient’s T cells from their blood using an outpatient procedure known as leukapheresis. These T cells are shipped to the laboratory for modification and manufacturing. The CAR-containing T cells are then returned for reinfusion into the patient. This process takes about 2 weeks. During the time that the cells are being developed, the patient will typically receive specific chemotherapy that can help prepare the immune system to support the CAR T cells once they are given back to the patient.
CAR T cells are administered in the hospital, where the patient can be monitored closely. Patients receiving CAR T-cell therapy typically develop temporarily low blood cell counts from the treatment, with fatigue, risk of infection, and need for transfusion support. Some patients may also have some of their normal immune cells, called B cells, destroyed as bystanders of the treatment, causing a condition called B-cell aplasia. Because B cells normally make antibodies to protect people from infections, people with B-cell aplasia need to have antibodies periodically given by vein.
In addition, there are 2 significant adverse effects that can occur after CAR T-cell therapy, both potentially serious: cytokine release syndrome (CRS) and neurologic complications. Patients with CRS typically develop a fever, rash, headache, and changes in blood pressure. The symptoms of neurologic toxic effects range from headaches to confusion, delirium, and seizures. Though the onset of the symptoms can occur within minutes or hours, they can be seen days to weeks later. The adverse effects are usually reversible, but rare cases of long-term symptoms have been noted. The possible long-term adverse effects may include cardiac dysfunction, bleeding, and kidney and/or liver failure. The management of severe CRS or neurotoxic effects may involve the use of specific drugs to reverse these symptoms.
CAR T-cell therapy has received preliminary approval for treatment of children and young adults with a specific form of leukemia that has not been cured with initial chemotherapy treatment. It is being studied in many other cancer treatment settings and may become more widely used based on the results of ongoing clinical research.
Published Online: September 7, 2017. doi:10.1001/jamaoncol.2017.2989
Conflict of Interest Disclosures: None reported.
Pagel JM, West H. Chimeric Antigen Receptor (CAR) T-Cell Therapy. JAMA Oncol. 2017;3(11):1595. doi:10.1001/jamaoncol.2017.2989
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