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What components and domains make up a chimeric antigen receptor (CAR)?
Chimeric antigen receptors (CARs) typically consist of an antigen-binding domain (ectodomain), a transmembrane domain, and intracellular (endodomain) immune receptor tyrosine-based activation motifs (ITAMs).2,3 The ectodomain typically consists of single chain variable fragment (scFv) composed of a light and a heavy variable monoclonal antibody fragment joined by a flexible linker. This structure determines receptor selectivity and affinity.2,3 The endodomain transmits activation signals to T cells upon antigen binding. More recently developed CARs have also incorporated co-stimulatory signaling domains in their ectodomains, allowing for both activation and co-stimulation signals to be transmitted simultaneously upon antigen binding.1,3
1. M. Sadelain, et al., “The basic principles of chimeric antigen receptor design,” Cancer Discov 3(4):388-398, 2013.
2. S. Yu, et al., “Chimeric antigen receptor T cells: a novel therapy for solid tumors,” J Hematol Oncol 10(1):78, 2017
3. G. Dotti, et al., “Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells,” Immunol Rev 257(1):10, 2014.
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