Questions and Answers About CAR T-Cell Therapy

One of the newest, most promising treatments for certain types of cancer is chimeric antigen receptor (CAR) T-cell therapy. A kind of immunotherapy, CAR T-cell therapy uses your body’s own immune system to help fight cancer.

Jonathan Serody, MD, is director of the UNC Health Cellular Therapy Program, and Natalie S. Grover, MD, is its clinical director. We asked these two leading experts in CAR T-cell therapy to answer some common questions people have about this treatment.

What Is CAR T-Cell Therapy?

We know the immune system can kill cancer cells, which has been demonstrated by the rise of immunotherapy in the treatment of cancer in the past decade. Immunotherapy uses your immune system to recognize foreign substances such as an infection (antigens), and your white blood cells work to destroy them.

Immunotherapy can use T-cells—the white blood cells normally responsible for killing cancerous cells—to help your immune system better act against cancer. That’s because T-cells have receptors that can recognize different proteins in the cancer cell.

For some patients, while this may initially work to attack cancer cells, eventually the cancer cells get sneaky and become harder for the body’s immune system to detect. In fact, they can look like normal, healthy cells, so the immune system may no longer send T-cells to fight them.

“The way the immune system kills cancer cells leaves it pretty susceptible to the cancer cell making changes that don’t allow it to be easily seen by the immune system,” Dr. Serody says.

When this happens, your care team will need a new way to help the body distinguish between healthy cells and cancer cells. This is when CAR T-cell therapy may be an option.

CAR T-cell therapy genetically engineers a patient’s T-cells in a laboratory by adding a protein called chimeric antigen receptor, or CAR. The CAR protein helps the T-cells find and kill cancer cells.

“CAR focuses on one specific protein marker that can be targeted,” Dr. Serody says. “So, all you would have to do is know that your tumor expressed the CAR antigen. And if it does, the CAR could work.”

In other words, these supercharged T-cells can tell the difference between cancer cells and healthy cells because they recognize the specific CAR protein markers on the cancer cells.

“The CAR T-cells now go to work hunting down and destroying the patient’s cancer,” Dr. Serody says.

CAR T-cell therapy can be effective against some types of cancer, especially when other treatments are not working. It is approved by the Food and Drug Administration to treat some blood cancers, including leukemia, lymphoma and multiple myeloma. There are also clinical trials underway to study its effectiveness in solid tumors.

How Does CAR T-Cell Therapy Work?

Most patients will receive autologous CAR T-cells, meaning the treatment uses their own immune cells, versus allogeneic, which uses T-cells from donor blood or umbilical cord blood.

Your blood will be collected one of two ways. Sometimes, if you have a sufficient number of lymphocytes in your bloodstream, your care team will draw your blood and ship it to a facility to isolate the T-cells and reprogram them with CAR proteins that will bind to your body’s cancer cells.

The other more common way is to connect you to a machine that circulates your blood, filters out T-cells and gives the rest of the blood back to you. The T-cells are then sent to a manufacturer to be created into CAR T-cells. This usually takes about three to four weeks.

“The T-cells are sent to the lab, where they supercharge them to make CAR T-cells and can manufacture millions of cells,” Dr. Grover says. “Then they get shipped back and infused into the patient.”

The infusion is like a blood transfusion, done through an IV in an outpatient or inpatient setting depending on the patient’s condition. It is usually a one-time treatment.

Before your infusion, you usually will have a short course of chemotherapy, so your immune system does not think the CAR T-cells are abnormal and reject them.

The chemotherapy essentially gives the body a head start in fighting the cancer cells, destroying normal cells so that the CAR cells will “have the run of the mill to proliferate” once a patient is infused, Dr. Serody says. This way, there will be lots of CAR cells available to kill the cancer.

“There is pretty good evidence that the effectiveness of CAR therapy is often related to how quickly they grow in the patient,” he says. “One way to make them grow faster is if they don’t have to compete with normal cells.”

What Are Common Side Effects of CAR T-Cell Therapy?

Because patients usually will have chemotherapy before getting a CAR T-cell infusion, they can experience side effects associated with chemotherapy, including nausea, vomiting and an increased risk of infection—making them immunocompromised.

A common and serious side effect of CAR T-cell therapy is cytokine release syndrome, or CRS. This is caused by an overactivation of the immune system.

“It’s basically the immune response to when the CAR T-cells expand,” Dr. Grover says. “Some patients can get infection-like symptoms like fevers and sometimes low blood pressure or low oxygen, usually a few days after infusion.”

CRS is treated with tocilizumab, a drug that targets one of the proteins that is increased in patients who have this side effect.

About a week after CAR T-cell infusion, some patients experience immune cell-associated neurotoxicity, which can cause headaches, confusion and speech problems. It also can cause seizures, brain swelling, and even coma or death.

“It can be complicated to manage,” Dr. Serody says. “We manage it with steroids, or a drug called anakinra.”

A third and much less common side effect is immune cell-associated hemophagocytic syndrome. This can cause “pretty significant systemic inflammation and also be challenging to treat,” Dr. Serody says.

Most of these side effects happen early—generally in the first two weeks or a month after infusion. “Depending on how severe your side effects are, that’s your recovery time,” Dr. Grover says.

Usually after three months, patients feel more like they did before they received the CAR T-cells.

“Increased risk of infection can last longer, so these patients can be more immunocompromised for a longer time—usually about a year,” Dr. Grover says.

You also cannot drive for eight weeks after CAR T-cell therapy because of the risk of seizures.

“The risk is low, but because of that, you will need to make sure you have caregiver support and transportation,” Dr. Grover says.

What Does CAR T-Cell Therapy Cost?

CAR T-cell therapy is a newer cancer treatment that may be more expensive than other therapies. Not all insurance plans cover CAR T-cell therapy. The out-of-pocket cost will depend on your insurance coverage. Most healthcare systems will work with you and your health insurance company to determine whether CAR T-cell therapy will be covered.

Want to know more about CAR T-cell therapy? Ask your doctor or learn more about CAR-T immunotherapy at UNC Health.