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What is CAR T-cell therapy?
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Chimeric antigen receptor T-cell therapy is a type of cancer treatment that utilizes a patient’s own immune cells to treat their cancer.
It is a relatively new technique and is currently only available in clinical trials.
Chimeric antigen receptor (CAR) T-cell therapy combines the targeting specificity of monoclonal antibodies and the cytotoxicity of cytotoxic T-cells. T cells are removed from the blood and genetically altered with CARs placed on their surface. The T cells are then multiplied and infused back into the patient’s blood, where they attack the cancer cells.
Data suggest CAR T-cell therapy has a significant antitumor effect specifically against neuroblastoma, chronic lymphocytic leukemia and B cell lymphoma.
Types of CARs
There are different types of CARs that are grouped into three generations.
The first-generation CARs involve antibody-based external receptor structures and cytosolic domains that encode signal transduction modules. These modules include an immunoreceptor tyrosine-based activation design, such as TCRζ or FcRγ. However, trials examining first-generation CARs have yielded disappointing results. The best data were reported after infusion of a GD2-specific CAR, in which only two of 11 patients experienced long-term remission from their cancer.
Therefore, second-generation CARs were created. These include a costimulatory signaling domain, such as CD28 or 4-1BB. Third-generation CARs are comprised of three or more cytosolic domains.
Common adverse events of CAR T-cell therapy include high fevers and significantly low blood pressure during the first days after treatment is administered.
Ongoing work
Future research aims include identifying optimal tumor targets and revealing and influencing both cell- and host-associated factors to support the increase in and persistence of genetically engineered cells. Another goal of research is to learn how to better manage the adverse events associated with CAR T-cell therapy. Many trials are currently ongoing to test second- and third-generation CARs for the treatment of a variety of other adult and pediatric cancer types.
For more information:
www.ncbi.nlm.nih.gov/pmc/articles/PMC4120077/
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