CAR T Cell Therapy

October 24, 2024

This page was reviewed under our medical and editorial policy by Alexis Boling, MSN-RN, CNML, director, nursing, Immune Effector Cell & Gene Therapy Program, City of Hope^® Cancer Center Duarte

The immune system protects the body by using cells that search for and destroy damaged or foreign cells. These immune cells have receptors that help them find threats to eliminate. However, cancer cells may hide from the immune system cells and grow uncontrollably.

Immunotherapy helps boost the immune system to detect and destroy cancer cells. Chimeric antigen receptor (CAR) T cell therapy, a type of immunotherapy, is an innovative approach that enhances the body’s ability to fight cancer.

What Is CAR T Cell Therapy?

CAR T cell therapy is an advanced treatment for certain cancers. It starts with the patient’s own T cells, a type of immune system cell. The T cells are collected from the patient and then modified to have a special receptor called a chimeric antigen receptor (CAR), which helps them target and destroy cancer cells. CAR T cell therapy is used for some blood cancers, such as chronic lymphocytic leukemia and acute lymphocytic leukemia. It is also being studied for other types of cancer, including solid tumors.

How Does CAR T Cell Therapy Work?

CAR T cell therapy is designed to boost the body’s immune response against cancer. It focuses on using the immune system to recognize and destroy cancer cells. In particular, CAR T cell therapy is a form of adoptive cell transfer. This means that the patient’s own immune cells are used to target the cancer.

At the core of CAR T cell treatment is the chimeric antigen receptor. This receptor is engineered to recognize and bind to specific proteins, known as antigens, on the surface of cancer cells. The relationship between antigens and immune receptors is like a lock and key: the appropriate receptor (key) may unlock the antigen (lock) on the cancer cell, enabling the immune system to attack.

CAR T cell therapy has been successful in treating blood cancers by targeting an antigen called CD19 that is found on these cancer cells. Each CAR is made to recognize a specific cancer antigen, so the therapy is tailored to the type of cancer being treated. The promising results with blood cancers have led to ongoing research to target antigens on solid tumors.

CAR T Cell Therapy Process

The CAR T cell therapy process takes several weeks and involves three main steps:

• Collecting T cells
• Modifying T cells in a laboratory
• Infusing modified T cells back into the patient

First, the patient undergoes a procedure called leukapheresis, in which the T cells are collected from the patient’s blood. This process takes about two to three hours. During this time, the patient lies in bed or reclines in a chair with two intravenous (IV) lines. Blood is drawn out through one IV line, the white blood cells (including T cells) are separated and the remaining blood is returned to the patient through a second IV. Some patients might experience numbness, tingling or muscle spasms during this procedure due to a drop in blood calcium levels, but this may be managed with calcium supplements.

Next, the collected T cells are sent to a laboratory, where they are genetically modified to produce chimeric antigen receptors (CARs). These receptors help the T cells target and attack cancer cells. The modified T cells — now called CAR T cells — are grown and multiplied in the laboratory over a few weeks.

Finally, once enough CAR T cells have been produced, they are infused back into the patient. Before this infusion, the patient may receive a mild form of chemotherapy. This reduces the number of other immune cells, giving the CAR T cells more room and a higher chance to fight the cancer. Once infused, the CAR T cells begin to target and destroy cancer cells. They also continue to multiply in the body to help target more cancer cells.

Outpatient CAR T Cell Therapy

Some patients may be candidates for outpatient CAR T cell therapy, which allows them to receive the treatment at an outpatient location rather than being admitted to the hospital. The process involves the same steps as the standard process, but leukapheresis, chemotherapy and the infusion are performed on an outpatient basis. The patient is closely monitored throughout the process to ensure they remain healthy and that no negative side effects occur.

CAR T Cell Therapy Side Effects

CAR T cell therapy may be appropriate for treating certain types of cancers, but it may also cause serious side effects. Many of these may be managed with medications, so patients should report them to their care team promptly.

One possible side effect is cytokine release syndrome (CRS). CAR T cells release chemicals called cytokines into the blood as they multiply, which may overstimulate the immune system. CRS may cause:

• Trouble breathing
• High fever
• Chills
• Headaches or dizziness
• Severe nausea, vomiting or diarrhea
• Elevated heart rate
• Extreme tiredness
• Joint and/or muscle pain

Another potential side effect involves the nervous system, leading to symptoms such as:

• Headaches
• Confusion
• Irritability
• Seizures
• Tremors
• Trouble speaking
• Trouble with balance

Patients are often advised not to drive or operate heavy machinery for several weeks after treatment due to these risks.

Other potential side effects include allergic reactions, abnormal blood levels of minerals or electrolytes, low blood counts and a higher risk of infections.

Cytokine Storm

Cytokine release syndrome, also known as CRS or a cytokine storm, is a common side effect of CAR T cell therapy. It happens when the CAR T cells release large amounts of chemicals called cytokines into the bloodstream. These cytokines may trigger a strong immune response, affecting multiple organs.

CRS may vary in severity. It often starts within the first week after the CAR T cell infusion and lasts about a week. Although CRS may be serious, it is usually reversible and may be managed with medications and close monitoring.

Several factors may increase the risk of CRS. These include having a high number of cancer cells, receiving a large number of CAR T cells and undergoing certain pre-treatment therapies. Blood tests measuring the number of cancer cells in the body (tumor burden), inflammatory markers and overall health may help predict the likelihood of CRS.

Researchers don’t completely understand what causes CRS. It is believed to be related to the interaction between tumor cells and immune cells, which releases cytokines like TNF-alpha and interferon-gamma. These, in turn, activate other immune cells to release more cytokines, creating a cycle of inflammation.

Health care providers are increasingly able to recognize and treat CRS early. The U.S. Food and Drug Administration (FDA) approved tocilizumab (Actemra^®) for this purpose.

What Happens If CAR T Cell Therapy Fails?

If CAR T cell therapy is not successful, several other treatment options may be considered. One possible approach is a second CAR T cell infusion. Research has shown that a second infusion of CAR T cells may be successful for some patients.

Another option is using bispecific antibodies, another type of immunotherapy. These antibodies have two receptors: one attaches to a T cell and another to a cancer cell. This dual attachment helps the T cells recognize and attack the cancer cells more successfully. They also might be an option for patients who are unable to receive CAR T cell therapy due to other health issues.

Other possible treatments if CAR T cell therapy is not successful include chemotherapy, targeted therapy, chemoimmunotherapy or radiation therapy for cancer that has not spread.

CAR T Cell Therapy at City of Hope

At City of Hope, our researchers are at the forefront of CAR T cell therapy research and innovations. Our clinicians are leaders in delivering best-in-class CAR T cell therapy on a global scale, performing the majority of our CAR T cell therapy in our Los Angeles-area location on an outpatient basis. Our scientists collaborate with other institutions to develop clinical trials to test new CAR T cell therapy options to help fight cancer and other diseases.

Learn more about our CAR T cell therapy research