What is Chimeric Antigen Receptor (CAR) T-Cell therapy?

From the Guidelines

CAR T-cell therapy is a revolutionary cancer treatment that uses genetically modified immune cells to fight cancer, and it is recommended for patients with certain blood cancers like leukemia, lymphoma, and multiple myeloma who have not responded to conventional therapies. The process involves collecting a patient's own T-cells, engineering them in a laboratory to express chimeric antigen receptors (CARs) on their surface, and then reinfusing these modified cells back into the patient 1. These CAR T-cells are specifically designed to recognize and attack cancer cells that have certain proteins on their surface. Currently approved CAR T-cell therapies include Kymriah (tisagenlecleucel), Yescarta (axicabtagene ciloleucel), Tecartus (brexucabtagene autoleucel), and Breyanzi (lisocabtagene maraleucel) 1.

Key Points to Consider

• The treatment typically involves a single infusion after chemotherapy preparation, known as lymphodepletion chemotherapy (LDC), which consists of fludarabine and cyclophosphamide 1.
• Patients should be aware that CAR T-cell therapy can cause serious side effects, including cytokine release syndrome (causing fever, low blood pressure) and neurological problems, which require close monitoring 1.
• The therapy works by enabling the immune system to specifically target cancer cells, providing a personalized approach to cancer treatment that has shown remarkable success in some patients who didn't respond to conventional therapies 1.
• Patient selection should be based upon the FDA-approved indications and eligibility criteria used in pivotal studies, and patients should be evaluated for uncontrolled infections, active graft-versus-host disease (GVHD), or recent donor-lymphocyte infusion (DLI) 1.

Important Considerations for Treatment

• CAR T-cell therapy is associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration, and multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes 1.
• The treatment has been associated with durable remission rates, and it is considered an exciting paradigm shift in anticancer therapy 1.
• Patients identified as candidates for CAR T cell therapy should rapidly be referred for financial counselling to avoid delays in accessing care related to insurance pre-authorizations 1.

From the Research

Definition of CAR T-Cell

• CAR T-cell therapy represents a major advancement in personalized cancer treatment, where a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen 2.
• Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient 3.
• CAR T cells are T lymphocytes that are genetically engineered to express a synthetic receptor that recognizes a tumor cell surface antigen and causes the T cell to kill the tumor cell 4.

Mechanism of CAR T-Cell

• CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains 3.
• The synthetic receptor binds to a tumor antigen, causing the T cell to kill the tumor cell 2.
• CAR T cells are then expanded for clinical use and infused back into the patient's body to attack and destroy chemotherapy-resistant cancer 2.

Applications of CAR T-Cell

• CAR T-cell therapy has shown promising results in the treatment of hematologic malignancies, including B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma 4.
• Six CAR T-cell products are approved by the US Food and Drug Administration (FDA) for 6 hematologic malignancies 4.
• Ongoing research is needed to improve the efficacy and safety of the therapy and expand its use to solid tumors 5.

Benefits and Risks of CAR T-Cell

• CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65% 4.
• The therapy has improved progression-free survival for multiple myeloma, improved overall survival for large B-cell lymphoma, and attained high rates of cancer remission for other hematologic malignancies 4.
• The high cost and the risk of cytokine release syndrome and neurotoxicity are limitations and potential side effects of CAR-T cell therapy 5.