What are CARs?
Chimeric antigen receptors (CARs) are recombinant receptor constructs composed of an extracellular single-chain variable fragment (scFv) derived from an antibody, joined to a hinge/spacer peptide and a transmembrane domain, which is further linked to the intracellular T cell signaling domains of the T cell receptor. CAR specificity for a target antigen comes from the extracellular domain. The intracellular domain is designed to replicate the normal series of events by which T cells are activated.1
CAR T cells are cellular biologics that combine CARs with an individual patient’s T cells to redirect T cell specificity to target a tumor-associated antigen in a human leukocyte antigen (HLA)–independent manner.2,3
How does CAR T cell therapy work?
CAR T cell therapy is thought to work by CAR recognition of tumor-associated antigens on antigen-expressing cells and which stimulates a T cell response. CARs can be designed to recognize an antigen on the surface of cells, such as the CD19, CD22 or BCMA markers on the surface of B cells. Because CAR T cell therapies recognize target antigens independent of HLA and provide their own co-stimulatory signaling, CAR T cells may have the potential to kill targeted malignant and normal antigen-expressing cells.1,4
In what tumor types is CAR T cell therapy being studied?
CAR T cell therapies are under investigation for the treatment of relapsed/refractory B cell malignancies, such as multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), among others.5-8 CAR T cell therapies have been approved for the treatment of: acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse in patients up to 25 years of age; and relapsed or refractory large B cell lymphoma after two or more lines of systemic therapy, including diffuse large B cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B cell lymphoma, and DLBCL arising from follicular lymphoma.5,6 CAR T cell therapy is also under investigation for acute myelogenous leukemia (AML), and several solid tumor types.9 Register to get additional information.
What is the process for developing and administering CAR T cell therapy?10
Development of CAR T cells begins with collection of the patient’s lymphocytes through apheresis. The CAR gene construct is inserted into the genome of the patient’s T cells through activation and transduction. CAR-expressing T cells are expanded, or grown, into a therapeutic dose. After conditioning therapy, the CAR T cells are administered into the patient, and the engineered T cells may multiply and provide activity against targeted cells and normal cells. The patient's healthcare team then monitors the patient for any signs of adverse reactions.
What toxicities have been associated with CAR T cell therapy in clinical trials?
Serious toxicities, requiring immediate medical attention and sometimes resulting in death, are known to occur with CAR T cell therapy. Toxicities have included, but are not limited to: cytokine release syndrome (CRS), neurotoxicities, and B cell aplasia—serious infections, prolonged cytopenias, and hypogammaglobulinemia. These are not all the side effects associated with CAR T therapies. The incidence and severity of toxicities differ from product to product.3,7