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. The premise of CAR T immunotherapy is to modify T cells to recognize cancer cells in order to more effectively target and destroy them. Scientists harvest T cells from people, genetically alter them, then infuse the resulting CAR T cells into patients to attack their tumors.
CAR T cells can be derived either from T cells in a patient's own blood (autologously) or from the T cells of another, healthy, donor (allogeneically). Once isolated from a person, 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 recipient's T cells to target an antigen that is present on the surface of tumors. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor but is not expressed on healthy cells.
After CAR T cells are infused into a patient, they act as a "living drug" against cancer cells. When they come in contact with their targeted antigen on a cell's surface, CAR T cells bind to it and become activated, then proceed to proliferate and become cytotoxic. 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.
The surface of CAR T cells can bear either of two types of co-receptors, CD4 and CD8.
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Ce cours décrit les mécanismes fondamentaux du système immunitaire pour mieux comprendre les bases immunologiques dela vaccination, de la transplantation, de l’immunothérapie, de l'allergie et des mal
Cancer immunotherapy (sometimes called immuno-oncology) is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology. Cancer immunotherapy exploits the fact that cancer cells often have tumor antigens, molecules on their surface that can be detected by the antibody proteins of the immune system, binding to them.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer (adoptive cell transfer). Serious side effects occur in most patients. The most common serious side effects are cytokine release syndrome (a potentially life-threatening condition that can cause fever, vomiting, shortness of breath, pain and low blood pressure) and decreases in platelets (components that help the blood to clot), hemoglobin (the protein found in red blood cells that carries oxygen around the body) or white blood cells including neutrophils and lymphocytes.
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