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Engineering high affinity, soluble T cell receptors for the treatment of cancer

      Background: T cell receptors (TCRs) bind short peptide fragments derived from endogenously processed proteins that are presented at the cell surface by human leukocyte antigens (HLAs). Natural cancer-specific TCRs have weak affinities for their cognate peptide-HLA (pHLA) complexes, preventing effective T cell mediated tumour clearance. At Immunocore we have developed a new class of bi-specifics, which comprise a soluble, high-affinity TCR targeting a specific cancer-associated pHLA, fused to an anti-CD3 scFv domain. These potent Immune mobilising monoclonal TCRs Against Cancer (ImmTAC) molecules can detect low peptide levels on cancer cells and recruit neighbouring T cells via CD3, leading to the targeted killing of malignant cells.
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