CAR T cell

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CAR T-cell Therapy

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CAR-Engineered T-Cell Adoptive Transfer

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CAR cartoon

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Depiction of 3 generations of CARs

Chimeric Antigen Receptor T-cell therapy (CAR T-cell therapy) is a type of immunotherapy that uses specially altered T cells—a part of the immune system—to fight cancer. This therapy modifies the patient's own T cells to attack cancer cells more effectively. CAR T-cell therapy has emerged as a breakthrough in the treatment of certain types of cancer, particularly B-cell malignancies such as acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL).

Overview

CAR T-cell therapy involves the collection of T cells from a patient's blood through a process called apheresis. In the laboratory, these cells are genetically engineered to produce special structures called chimeric antigen receptors (CARs) on their surface. CARs are designed to recognize and bind to specific proteins (antigens) on the surface of cancer cells. Once the T cells are modified to express CARs, they are expanded in the laboratory to create millions of these cells. The expanded population of CAR T cells is then infused back into the patient. Once inside the patient's body, these engineered T cells multiply and attack cancer cells that have the target antigen on their surface.

Mechanism of Action

The mechanism of action of CAR T-cell therapy involves several key steps: 1. Identification of Target Antigen: A specific antigen that is predominantly expressed on the surface of cancer cells, but not on normal cells, is identified. This antigen serves as the target for the CAR T cells. 2. T Cell Modification: Patient's T cells are collected and genetically modified in the laboratory to express CARs that can recognize and bind to the target antigen. 3. Expansion: The genetically modified T cells are cultured in the laboratory to increase their numbers. 4. Infusion: The expanded CAR T cells are infused back into the patient. 5. Activation and Proliferation: Once infused, the CAR T cells begin to recognize and bind to cancer cells through the specific antigen, become activated, and kill the cancer cells. The CAR T cells also proliferate, increasing their numbers in the patient's body to continue attacking the cancer cells.

Applications

CAR T-cell therapy has been approved for use in several types of cancer, including: - Acute Lymphoblastic Leukemia (ALL) in children and young adults. - Diffuse Large B-Cell Lymphoma (DLBCL) in adults. - Certain types of multiple myeloma.

Risks and Side Effects

While CAR T-cell therapy has shown promising results, it can also cause significant side effects, including: - Cytokine Release Syndrome (CRS): A systemic inflammatory response caused by the rapid proliferation of CAR T cells, leading to fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. - Neurotoxicity: Also known as immune effector cell-associated neurotoxicity syndrome (ICANS), symptoms can range from confusion and agitation to seizures and coma. - B-cell Aplasia: Since CAR T cells can target normal B cells that express the target antigen, this can lead to a decrease in normal B cells, resulting in an increased risk of infections.

Future Directions

Research is ongoing to expand the use of CAR T-cell therapy to other types of cancer and to improve the safety and efficacy of the treatment. Efforts include developing CAR T cells that target different antigens, reducing side effects, and making the therapy more accessible and cost-effective.