CAR T-cell Therapy for Lung Cancer

What Is CAR T-cell Therapy?

A form of lung cancer treatment, CAR T-cell therapy is a targeted therapy that works to enhance the patient’s immune system for fighting tumors. This kind of treatment boosts the immune system by modifying its T-cells, otherwise characterized as white blood cells (i.e., immunity cells in the bloodstream attacking bacteria, viruses, etc.), to fight a specific type of cancer.

To date, only a few CAR T-cell therapy medications have been approved by the Food and Drug Administration (FDA) to treat some lymphomas and leukemia. The approved therapies include:

• Axicabtagene ciloleucel (Yescarta®)
• Brexucabtagene autoleucel (Tecartus®)
• Tisagenlecleucel (Kymriah®)

Because cancer cells came from healthy cells, they are often able to hide from white blood cell attacks. CAR T-cell therapy removes some of the blood’s T-cells and modifies them in a special laboratory before reinserting them into the bloodstream. The modified T-cells contain new receptors (known as chimeric antigen receptors, or CAR) that are better able to differentiate cancer cells from healthy ones.

While non-small cell and small cell lung cancers tend to have poor prognoses, immunotherapies have been able to improve outcomes for certain patients. Today, the development of CAR T-cell cancer treatments has increased cancer-killing effects of treatment, prolonged survival times, and reduced side effects.

How Does CAR T-cell Therapy Work?

The American Cancer Society describes the connection between antigens and immune receptors within the immune system as a lock-and-key arrangement. Immune receptors need the right “key” on the surface of T-cells to bind to the foreign antigens that don’t belong in the body. Without the correct receptors, T-cells can’t attach to cancer cells’ antigens or kill them.

CAR T-cells are manmade and, when reinserted into the body, are better able to locate cancer cells throughout the body. However, this is an individualized cancer treatment. CAR T-cells that fight non-small cell lung cancers are not likely to be effective against small cell lung cancers. Consequently, each type of cancer cell requires a different antigen receptor (i.e., a different procedure).

CAR T-cell Treatment Process

The treatment process for therapy involves several steps and lasts some months from assessment to recovery. The steps below detail the general procedure patients undergoing CAR T-cell therapy can expect.

1. Assessment: Doctors assess the suitability of therapy for patients depending on their overall health and type of cancer. This may include health screenings or diagnostic tests.
2. Collection: Using two intravenous (IV) lines connected to a separating machine, blood is removed from the body. The T-cells are separated from the blood, and the remaining blood is sent back to the body through the second IV.
3. Production: In a special laboratory, the patient’s T-cells are modified to fight their type of cancer. Too, the new CAR T-cells are multiplied using an “expanding” process into millions of CAR T-cells in preparation to rejoin the circulatory system.
4. Chemotherapy: Normally, patients are given a round of chemo prior to a CAR T-cell infusion to lower the number of existing immune cells, giving them a greater chance of being effective.
5. Procedure: CAR T-cell infusions are given via IV in an inpatient hospital procedure. Though the procedure takes only a few hours, patients are monitored afterward for extreme immune responses requiring emergency medical attention.
6. Recovery: Full recovery may take between two and three months as the CAR T-cells fight cancer cells throughout the body. During this time, side effects and other possible complications are monitored closely.

Side Effects and Complications

The most common side effects are caused by the normal action of the new T-cells in the immune system. As CAR T-cells spread throughout the body, the immune system releases cytokines into the bloodstream. Cytokine release syndrome (CRS) can feel similar to a case of the flu (ranging in severity from mild to severe).

CRS causes side effects such as:

• Chills
• Diarrhea
• Fatigue
• High fever
• Increased heart rate
• Loss of appetite
• Low blood pressure
• Muscle aches
• Nausea
• Shortness of breath
• Trouble seeing
• Vomiting

CRS is treated by managing symptoms with medication and fluids. The patient is also closely monitored for any new or worsening symptoms.

In addition to immune effects, neurologic complications are often among the common complications. For some patients, these effects can be serious. Complications include:

• Agitation
• Altered consciousness
• Brain swelling
• Confusion
• Difficulty speaking
• Difficulty understanding
• Encephalopathy
• Loss of balance
• Seizures
• Severe headaches

Can CAR T-cell Therapy Treat Lung Cancer?

Yes. CAR T-cell therapy can be used to treat lung cancers as well as other cancers of the respiratory system. Because the therapy is individualized to the patient’s cancer, treatment may be more effective and produce fewer, painful side-effects than procedures like radiation therapy or chemotherapy. (Although some targeted chemotherapies like HIPEC usually carry fewer side effects.)

To date, CAR T-cell therapy has not been approved by the FDA to treat lung cancer. Patients can find open clinical trials for these therapies by talking with the doctor or visiting the ClinicalTrials.gov page.