Chimeric antigenic receptor (CAR) T-cell therapy is a novel type of immunotherapy approved by the U.S. Food and Drug Administration (FDA) to treat certain types of cancer, including lymphomas. The approach takes the patient’s own immune cells and genetically modifies them in the laboratory so that they become more efficient and lethal to cancer cells.
How does CAR T-cell therapy work?
CAR T-cell therapy involves several steps. The first is the separation of a type of cancer-fighting immune cell called T-cells from the patient’s blood. These cells are then genetically modified in the laboratory to improve their ability to identify and efficiently kill cancer cells. This is achieved by altering receptors expressed on the surface of these T-cells, turning them into so-called chimeric antigenic receptors (CAR), which can better recognize cancer cells in the body and become activated to kill them. The CAR T-cells are then allowed to grow and multiply.
Then, the patient is subjected to a brief course of chemotherapy so that their immune system does not attack and kill the CAR T-cells. After chemotherapy, the CAR T-cells are delivered into the patient’s body by infusion. These cells multiply and specifically recognize a cell surface protein abundantly found on the surface of cancer cells called the CD19 antigen. Once the CAR T-cells attach to the cancer cells, they get activated to kill them.
The advantage of CAR T-cell therapy is that these cells remain in the body for a long time and hence can help fight cancer again if it returns.
FDA-approved CAR T-cell therapies for lymphomas
Two FDA-approved therapies are currently available for lymphoma patients who do not respond to any other treatment.
Yescarta (axicabtagene ciloleucel), developed by Kite Pharma, is approved to treat aggressive, relapsed and/or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, and transformed follicular lymphoma.
Other CAR T-cell therapies in the pipeline
KTE-X19 is an investigational CAR T-cell therapy being developed by Kite Pharma that is awaiting approval by the FDA and European Medicines Agency (EMA) for the treatment of adult patients with refractory or relapsed mantle cell lymphoma (MCL).
It has been granted the designations of breakthrough therapy by the FDA and priority medicines by the EMA for relapsed or refractory MCL.
CAR T-cell therapy is a highly specialized and personalized treatment. It is only available at a limited number of specialized cancer centers.
The most common side effects of CAR T-cell therapy include:
- Cytokine release syndrome, where patients show flu-like symptoms such as headaches, fever, chills, severe nausea, vomiting, diarrhea, severe muscle or joint pain, shortness of breath, low blood pressure, and fast heart rate. These symptoms may be mild, but in a few patients, they can be serious and life-threatening.
- Neurologic adverse events such as encephalopathy, confusion, aphasia (difficulty in understanding or speaking), drowsiness, agitation, seizures, loss of balance, and altered consciousness. These symptoms are temporary in most patients but more serious and long-lasting in a few.
- Blood-related symptoms such as neutropenia and anemia.
Last updated: Feb. 4, 2020
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