8f0l

Crystal Structure of the Human T cell Receptor CD3(EPSILON) N-Terminal Peptide Complexed with ADI-26906 FAB

spinqualitylabelsall models 8f0l, resolution 1.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8f0l 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 1.81Å Ligands: GOL, PCA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Bispecific antibodies continue to represent a growth area for antibody therapeutics, with roughly a third of molecules in clinical development being T-cell engagers that use an anti-CD3 binding arm. CD3 antibodies possessing cross-reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N-terminus of CD3 epsilon (CD3epsilon). Such antibodies have high isoelectric points and display problematic polyreactivity (correlated with poor pharmacokinetics for monospecific antibodies). Using insights from the crystal structure of anti-Hu/Cy CD3 antibody ADI-26906 in complex with CD3epsilon and antibody engineering using a yeast-based platform, we have derived high-affinity CD3 antibody variants with very low polyreactivity and significantly improved biophysical developability. Comparison of these variants with CD3 antibodies in the clinic (as part of bi- or multi-specifics) shows that affinity for CD3 is correlated with polyreactivity. Our engineered CD3 antibodies break this correlation, forming a broad affinity range with no to low polyreactivity. Such antibodies will enable bispecifics with improved pharmacokinetic and safety profiles and suggest engineering solutions that will benefit the large and growing sector of T-cell engagers. Structure-based engineering of a novel CD3epsilon-targeting antibody for reduced polyreactivity.,Liu CY, Ahonen CL, Brown ME, Zhou L, Welin M, Krauland EM, Pejchal R, Widboom PF, Battles MB MAbs. 2023 Jan-Dec;15(1):2189974. doi: 10.1080/19420862.2023.2189974. PMID:36991534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also T-cell receptor 3D structures

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