Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary breakthrough in immunotherapy for cancer treatment. By genetically modifying certain infection-fighting white blood cells (T-cells), this cutting-edge technique can harness the power of the body’s own immune system to recognize and attack cancer cells with a high level of precision.
As part of our commitment to providing world-class cancer care, Tampa General Hospital’s Cancer Institute established an adult Bone Marrow Transplant (BMT) and Cell Therapies Unit. In addition to hematology oncologists with extensive training in bone marrow transplantation and immunotherapy, our multidisciplinary team includes experienced nurse practitioners, nurse navigators, social workers, counselors, dietitians, and physical therapists. Together, we provide holistic care for patients with aggressive hematological malignancies.
What are Antigens?
Antigens are proteins that are recognized by the immune system. Different cancers have different antigens and each cancer cell can have many antigens present on its surface. Cancer cells may have antigens that T-cells can recognize, target, and kill.
What are T-cells?
As an essential component of the body’s immune system, T-cells continually seek out and fight infections and foreign substances throughout the body. Each T-cell has receptors that recognize certain proteins (antigens). When an abnormal or foreign antigen is detected, the immune system destroys it.
What are CAR T-cells?
CAR T-cells stand for Chimeric Antigen Receptor T-cells. These are an individual’s T-cells that have been genetically modified by the CAR to recognize and destroy specific cancer cells. The CAR is inserted into the T-cells during a manufacturing process which can take 3-4 weeks. The receptor on the CAR T-cell attaches to the antigen on the cancer cell, activates the T-cell, and destroys the cancer cell. CAR T-cell therapy is highly specialized, and each type is designed to target a specific cancer antigen.
What Types of Cancer Can Be Treated With CAR T-cell Therapy?
CAR T-cell therapy is currently approved by the U.S. Food and Drug Administration (FDA) as the standard of care for certain types of lymphoma, multiple myeloma, and leukemia, including:
- Diffuse large B cell lymphoma
- Primary mediastinal B cell lymphoma
- High-grade B cell lymphoma
- Mantle cell lymphoma
- Transformed follicular lymphoma
- Relapsed or refractory follicular lymphoma
- Relapsed or refractory multiple myeloma
- Relapsed or refractory acute lymphoblastic leukemia
In ongoing CAR T-cell therapy clinical trials, the effectiveness of this promising treatment option for other types of blood cancer, solid tumors, and nonmalignant conditions is being evaluated in comparison to the current standard of care.
CAR T-cell Therapy Process
The CAR T-cell therapy process, which takes approximately three months to complete, involves several steps:
Patient Evaluation
The patient is thoroughly screened through a series of medical tests to determine if they are a good candidate for CAR T-cell therapy. During this assessment, the treatment team will consider factors such as the patient’s age, overall health, organ function, and living situation.
T-cell Collection
T-cells are collected from the blood by a process called leukapheresis. Blood is drawn from a temporary catheter placed in a large vein. This catheter is placed in the morning prior to collection and removed after collection on the same day. The blood flows through tubing connected to an apheresis machine, which separates the T-cells from other blood components. The isolated T-cells are collected and the remaining blood components are returned to the patient.
T-cell Modification
Following collection, the T-cells are sent to a manufacturing facility where they are modified or “engineered” by adding a man-made CAR designed to target a specific cancer antigen. These modified cells are then called CAR T-cells. The CAR T-cells are expanded in the laboratory until there are millions of them. They are frozen and sent back to the hospital to be infused into the patient. The manufacturing process can take 3 to 4 weeks or more to complete. Because this is a long process, some patients may receive “bridging” chemotherapy to temporarily control the cancer until the CAR T-cells are ready.
Lymphodepleting Chemotherapy
Once the CAR T-cells return to the hospital, the patient will receive chemotherapy to prepare the body for receiving the cells. The chemotherapy will reduce the number of normal T-cells in the body to make room for the CAR T-cells to better expand and grow. This is called lymphodepletion.
CAR T-cell Infusion
The CAR T-cells are kept frozen until they are ready to be infused. The CAR T-cells are then thawed and infused into the patient via a central line. The process is similar to a blood transfusion and typically takes 30 minutes or less to complete. The patient is given medication to help prevent and control possible side effects during the infusion.
Observation and Recovery
After the CAR T-cells are infused, the patient will be closely monitored at the hospital for 10-14 days after the infusion for acute toxicities that may occur. Patients will be closely followed by the Cell Therapy team for two to three months on an out-patient basis while their immune system recovers. During the recovery period, the treatment team will evaluate the patient’s response to the CAR T-cell therapy and any side effects or complications. Patients are required to live within a certain radius of the hospital for at least 4 weeks after the CAR T infusion and are unable to drive for at least 8 weeks following the infusion.
What to Expect With CAR T-cell Therapy
CAR T-cell therapy can sometimes cause an overly robust immune system response that triggers the release of too many inflammatory molecules called cytokines. These cytokines are chemical messengers that signal the immune system to fight an invader. While normal cytokine release is beneficial, excessive cytokine release can lead to cytokine-associated toxicity. Also known as cytokine release syndrome (CRS), this condition can cause symptoms that range in severity from mild to severe, such as:
- Fever and chills
- Overwhelming fatigue
- Nausea, vomiting, and diarrhea
- Dizziness, lightheadedness, and headaches
- Low blood pressure
- Rapid heartbeat
- Joint and muscle pain
- Bleeding
- Shortness of breath
CAR T-cell therapy can also affect the body’s nervous system, which can lead to confusion, difficulty speaking or slurred speech, tremors, and loss of balance or coordination. This is referred to as Immune Effector Cell-Associated Neurotoxicity (ICANS).
In our BMT and Cellular Therapies Unit, our team of experts closely monitor the patient during their recovery period, and the treatment team can identify and help manage any side effects or complications of CAR T-cell therapy. For instance, corticosteroids or drugs that target specific cytokines may be considered to reduce inflammation.
Effectiveness of CAR T-cell Therapy
CAR T-cell therapy has proven to be highly effective in treating certain hematological malignancies, often achieving a deep and durable response in patients who have not responded to traditional treatments, such as chemotherapy and stem cell transplantation. It has been particularly successful in addressing certain forms of lymphoma, multiple myeloma, and leukemia.
With that said, it is important to note that the effectiveness of CAR T-cell therapy can vary widely depending on factors such as the type of cancer and the patient’s overall health. Through ongoing research and clinical trials, scientists and clinicians continue to explore the application of CAR T-cell therapy in different cancer types and improve its efficacy.
Benefit From World-Class Care at TGH
CAR T-cell therapy is a highly specialized and personalized cancer treatment available only at a select few hospitals and cancer centers around the world. TGH is proud to offer FDA-approved CAR T-cell therapies as well as CAR T-cell therapy clinical trials, including advanced immunotherapy options for even the most complex cases. Our scientists and clinicians continue to advance the field by investigating and developing new CAR T-cell therapies and expanding their use.
If you would like to learn more about CAR T-cell therapy, contact TGH at (813) 844-4151 to request an appointment with an expert in our BMT and Cell Therapies Unit.