T cells genetically engineered to express chimeric antigen receptors (CARs) represent
a promising approach in cancer immunotherapy. CARs consist of an extracellular binding
moiety providing antigen specificity and an intracellular signaling domain derived
from an activating immune receptor. Both are linked via a hinge and transmembrane
domain. Introducing co-stimulatory domains, such as CD28 or CD137, can enhance signaling.
Although, CAR T cells showed encouraging clinical results in patients with B cell
malignancies, major drawbacks include on-target off-tumor effects or severe cytokine
release syndrome (sCRS).
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