Chimeric antigen receptor T cell production and infusion: 1. T cells are isolated from a patient's blood 2. A new gene encoding a chimeric antigen receptor is incorporated into the T cells 3. Engineered T cells are now specific to a desired target antigen 4. Engineered T cells are expanded in tissue culture 5. Engineered T cells are infused back into the patient
In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.
CAR T cell therapy uses T cells engineered with CARs to treat cancer. T cells are modified to recognize cancer cells and destroy them. The standard approach is to harvest T cells from patients, genetically alter them, then infuse the resulting CAR T cells into patients to attack their tumors.[1]
CAR T cells can be derived either autologously from T cells in a patient's own blood or allogeneically from those of a donor. Once isolated, these T cells are genetically engineered to express a specific CAR, using a vector derived from an engineered lentivirus such as HIV (see Lentiviral vector in gene therapy). The CAR programs the T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor cell but not on healthy cells.[2]
After the modified T cells are infused into a patient, they act as a "living drug" against cancer cells.[3] When they come in contact with their targeted antigen on a cell's surface, T cells bind to it and become activated, then proceed to proliferate and become cytotoxic.[4] CAR T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity), and by causing the increased secretion of factors that can affect other cells such as cytokines, interleukins and growth factors.[5]
The surface of CAR T cells can bear either of two types of co-receptors, CD4 and CD8. These two cell types, called CD4+ and CD8+, respectively, have different and interacting cytotoxic effects. Therapies employing a 1-to-1 ratio of the cell types apparently provide synergistic antitumor effects.[6]
^Fox M (July 12, 2017). "New Gene Therapy for Cancer Offers Hope to Those With No Options Left". NBC News.
^Cite error: The named reference Sadelain2013 was invoked but never defined (see the help page).
^Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ (September 2017). "Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts". EMBO Molecular Medicine. 9 (9): 1183–1197. doi:10.15252/emmm.201607485. PMC 5582407. PMID 28765140.
^Tang XJ, Sun XY, Huang KM, Zhang L, Yang ZS, Zou DD, et al. (December 2015). "Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy". Oncotarget. 6 (42): 44179–44190. doi:10.18632/oncotarget.6175. PMC 4792550. PMID 26496034.
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