The chimeric antigen receptors (CARs) have emerged as a useful tool to redirect T cells. However, despite very potent, CAR is limited to recognize membrane proteins which only comprise around 1% of the total proteins. There are plenty of attractive tumor antigens arising from intracellular proteins. TCR-like antibodies, which allow for specific targeting of intracellular proteins via MHC/peptide complexes, appear as an unexploited opportunity for antibody therapies. Therefore, introduction of an antigen-binding fragment from TCR-like antibody to CAR, termed TCR-like CAR, will breakthrough the antigen limitation of CAR and combines the benefits of both. Our TCR-like CAR opens therapeutic avenues not only conserving the specificity and the functionality of the original TCR-like antibody, but also performing T cell signaling for cellular functions.
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