Five things you should know about CAR T-cell therapy

A scientist holding and observing a vile in the lab
This emerging form of immunotherapy uses a patient's own re-engineered T-cells to attack cancer.

When the U.S. Food and Drug Administration (FDA) approved a new leukemia treatment last year, a 12-year-old named Emily Whitehead was there to witness the historic announcement. Six years earlier, Emily was near death when her parents enrolled her in a clinical trial on a novel cancer treatment called CAR T-cell therapy. This emerging form of immunotherapy uses a patient's own re-engineered cells to attack cancer. Today, Emily, the first pediatric patient to receive CAR T-cell therapy, has no evidence of disease, like dozens of others who have since undergone the treatment. “We’re saving patients who three or four years ago we were at our wit’s end trying to keep alive,” Stephen Schuster, MD, an oncologist at Penn Medicine, told The Washington Post about CAR T-cell therapy.

Despite the optimism, though, it’s important to know that CAR T-cell therapy has significant downsides: It’s not available to most patients, its approvals have strict limitations, and it often triggers serious side effects in some patients.

Many cancer therapies work by triggering cells to attack cancer. CAR T-cell therapy removes a patient's T-cells, the white blood cells that are key to immune function, then modifies them in a lab and infuses them back into the patient’s body. The re-engineered T-cells are designed to recognize and attack cancer cells. The American Society of Clinical Oncology (ASCO) named the treatment its Advance of the Year for 2018. "A new and unique new way to treat cancer, CAR T-cell therapy is poised to transform the outlook for children and adults with certain otherwise incurable cancers," ASCO said in a statement.  

CAR (chimeric antigen receptor) is named for the chimera, a mythical creature made from the parts of different animals—the head of a lion, the body of a goat. True to their name, CAR T-cells have key extra parts on their surface: manmade cell receptors that are designed to attach themselves to cancer cells and kill them. "I'm extremely excited about the potential for CAR T-cell therapy," says Alan Tan, MD, Medical Director of Hematology & Immunotherapy and Medical Oncologist and Hematologist at our hospital near Phoenix. "This is a major landmark in how we may treat many cancers in the future."

I'm extremely excited about the potential for CAR T-cell therapy. This is a major landmark in how we may treat many cancers in the future.” - Alan Tan, MD, - Medical Oncologist and Hematologist

Here are five things you should know about CAR T-cell therapy:

It is only approved to treat a small number of patients.

The treatment has been approved to treat just two cancers to date: leukemia and non-Hodgkin lymphoma. And both approvals significantly limit the type of patients who can undergo the treatment:

  • Tisagenlecleucel (Kymriah®) is approved as a treatment option for acute lymphoblastic leukemia (ALL) in patients 25 and younger who have a recurrent cancer or whose disease is resistant to treatment. According to the National Cancer Institute, more than 50 percent of all new ALL cases occur in patients younger than 20.
  • Axicabtagene ciloleucel (Yescarta®) is approved as a treatment option for adult patients with large B-cell non-Hodgkin lymphoma, and only if their cancer has returned or their disease has not responded after at least two other types of treatment.

It seems to work better on blood cancers.

CAR T-cell therapy has been approved only for blood cancers, and clinical trials measuring its performance on solid tumors have not been encouraging.  CAR T-cells treat leukemia by targeting a specific type of B-cell (white blood cells that produce infection-fighting antibodies). But many solid tumors have multiple genomic mutations that drugs may try to target in prompting an immune response, and identifying the one target driving the tumor's growth is difficult. Also, some solid tumors recruit immune cells to perform destructive behaviors, often making the tumor more resistant to treatment. "The difficulty with solid tumors is, what do you target and how do you program that target into the T-cell?” Dr. Tan says. “That's going to take some time." 

CAR T-cell therapy may cause severe side effects.

The side effects of CAR T-cell therapy, especially a condition known as cytokine release syndrome (CRS), may be life-threatening. Cytokines are proteins that help regulate the immune system. In some cases, CAR T-cell therapy patients are flooded with cytokines that begin to attack healthy cells and tissue, resulting in flu-like symptoms, high fever, life-threatening neurological side effects and other serious conditions. The FDA requires that hospitals that use CAR T-cell therapy have staff certified and trained to recognize and manage CRS. CAR T-cells may also attack healthy B-cells, increasing the risk of infections in some patients.

It takes weeks for the full treatment to be completed.

The process of making CAR T-cells is extremely complex. After the T-cells are removed from the bloodstream, they are frozen and shipped to a lab. There, the T-cells are processed, re-engineered, reproduced, frozen again and shipped back to be reinfused in the patient. From start to finish, the process may take up to three weeks. The complexity of the process has limited the treatment's availability and has raised questions as to whether it can be reproduced on a larger scale so it can be made available to more patients.

CAR T-cells are designed to work forever.

When T-cells attack harmful cells or viruses, they are programmed to remember them if they attack again. CAR T-cells are no different. If the process works correctly, they are meant to be on 24/7 duty for the rest of the patient's life. Theoretically, if cancer cells re-emerge, the CAR T-cells will recognize them and kill them, even without the patient knowing it. "CAR-T cells are designed to have long-lasting effects with one treatment," Dr. Tan says. "In general, once you infuse the engineered T-cells, they remain in your body. It’s akin to having a 'living drug' in your body for the rest of your life."

Learn more about leukemia and non-Hodgkin lymphoma