From the Guidelines
CAR T cells are genetically reprogrammed T cells that express chimeric antigen receptors (CARs), which are synthetic receptors designed to target tumor surface antigens, making them a type of adoptive cell therapy and a "living drug". This treatment is primarily used for certain blood cancers like leukemia, lymphoma, and multiple myeloma, particularly when other treatments have failed 1. The process involves collecting T cells from a patient's blood, engineering them in a laboratory to produce CARs on their surface, multiplying them, and then infusing them back into the patient to seek out and destroy cancer cells.
Some key points about CAR T cell therapy include:
- It is a form of immunotherapy that harnesses the body's own immune system to target cancer more precisely than traditional treatments 1.
- The treatment can cause side effects, including cytokine release syndrome and neurological problems, which require careful monitoring 1.
- CAR T cell therapy offers potential for long-term remission in some patients but is not suitable for all cancer types and is typically reserved for specific situations where its benefits outweigh the risks 1.
- The therapy works by merging the specificity of an antibody with the cytotoxic and memory functionality of T cells, inducing a potent antitumor immune response 1.
The management of CAR T cell-related toxicities is crucial, and guidelines such as those from the National Comprehensive Cancer Network (NCCN) provide recommendations for managing these toxicities in patients with cancer based on available evidence and clinical experience 1. Similarly, the American Society of Clinical Oncology (ASCO) has guidelines for managing immune-related adverse events in adult patients with cancer treated with CAR T-cell therapy 1. Overall, CAR T cell therapy is a promising treatment option for certain types of blood cancers, but its use requires careful consideration of the potential benefits and risks.
From the Research
Definition of CAR T Cell
- CAR T cell therapy involves genetic modification of a patient's autologous T-cells to express a Chimeric Antigen Receptor (CAR) specific for a tumor antigen 2
- 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 2
- The genetic modification of T-cells may occur via viral-based gene transfer methods or nonviral methods, such as DNA-based transposons, CRISPR/Cas9 technology, or direct transfer of in vitro transcribed-mRNA by electroporation 2
Mechanism of Action
- CAR T cells recognize and kill tumor cells by expressing a synthetic receptor that recognizes a tumor cell surface antigen 3
- The activation of CAR T cells leads to the release of cytokines and the elimination of tumor cells 4, 5
Clinical Applications
- CAR T cell therapy is approved for the treatment of hematological malignancies, including B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, and multiple myeloma 4, 5, 6, 3
- Clinical trials have shown promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia 2
- CAR T cell therapy has improved overall survival for patients with large B-cell lymphoma and progression-free survival for patients with multiple myeloma 3
Challenges and Limitations
- The effective translation of CAR T-cell therapy to solid tumors is limited due to therapeutic barriers, such as CAR T-cell expansion, persistence, trafficking, and fate within tumors 2
- CAR T cell therapy is associated with significant side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4, 5, 6, 3