7su0

Crystal structure of an acidic pH-selective Ipilimumab variant Ipi.105 in complex with CTLA-4

spinqualitylabelsall models 7su0, resolution 2.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7su0 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 2.41Å Ligands: FLC, NAG, PCA, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although therapeutically efficacious, ipilimumab can exhibit dose-limiting toxicity that prevents maximal efficacious clinical outcomes and can lead to discontinuation of treatment. We hypothesized that an acidic pH-selective ipilimumab (pH Ipi), which preferentially and reversibly targets the acidic tumor microenvironment over the neutral periphery, may have a more favorable therapeutic index. While ipilimumab has pH-independent CTLA-4 affinity, pH Ipi variants have been engineered to have up to 50-fold enhanced affinity to CTLA-4 at pH 6.0 compared to pH 7.4. In hCTLA-4 knock-in mice, these variants have maintained anti-tumor activity and reduced peripheral activation, a surrogate marker for toxicity. pH-sensitive therapeutic antibodies may be a differentiating paradigm and a novel modality for enhanced tumor targeting and improved safety profiles. Improved therapeutic index of an acidic pH-selective antibody.,Lee PS, MacDonald KG, Massi E, Chew PV, Bee C, Perkins P, Chau B, Thudium K, Lohre J, Nandi P, Deyanova EG, Barman I, Gudmundsson O, Dollinger G, Sproul T, Engelhardt JJ, Strop P, Rajpal A MAbs. 2022 Jan-Dec;14(1):2024642. doi: 10.1080/19420862.2021.2024642. PMID:35192429 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures CTLA-4

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