7re8 | pdb_00007re8

Class I MHC (HLA-A*02) presenting alpha fetoprotein peptide (AFP)

spinqualitylabelsall models 7re8, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7re8 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.82Å Ligands: 1PE, PEG, PGE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5B8RNS7_HUMAN Publication Abstract from PubMed Monoclonal antibodies are at the vanguard of the most promising cancer treatments. Whereas traditional therapeutic antibodies have been limited to extracellular antigens, T cell receptor mimic (TCRm) antibodies can target intracellular antigens presented by cell surface major histocompatibility complex (MHC) proteins. TCRm antibodies can therefore target a repertoire of otherwise undruggable cancer antigens. However, the consequences of off-target peptide/MHC recognition with engineered T cell therapies are severe, and thus there are significant safety concerns with TCRm antibodies. Here we explored the specificity and safety profile of a new TCRm-based T cell therapy for hepatocellular carcinoma (HCC), a solid tumor for which no effective treatment exists. We targeted an alpha-fetoprotein peptide presented by HLA-A*02 with a highly specific TCRm, which crystallographic structural analysis showed binds directly over the HLA protein and interfaces with the full length of the peptide. We fused the TCRm to the gamma and delta subunits of a TCR, producing a signaling AbTCR construct. This was combined with an scFv/CD28 co-stimulatory molecule targeting glypican-3 for increased efficacy towards tumor cells. This AbTCR + co-stimulatory T cell therapy showed potent activity against AFP-positive cancer cell lines in vitro and an in an in vivo model and undetectable activity against AFP-negative cells. In an in-human safety assessment, no significant adverse events or cytokine release syndrome were observed and evidence of efficacy was seen. Remarkably, one patient with metastatic HCC achieved a complete remission after nine months and ultimately qualified for a liver transplant. Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma.,Liu C, Liu H, Dasgupta M, Hellman LM, Zhang X, Qu K, Xue H, Wang Y, Fan F, Chang Q, Yu D, Ge L, Zhang Y, Cui Z, Zhang P, Heller B, Zhang H, Shi B, Baker BM, Liu C Sci Rep. 2022 Jul 15;12(1):12068. doi: 10.1038/s41598-022-15946-5. PMID:35840635 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures MHC 3D structures MHC I 3D structures

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