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Seung Beom Choi,Nahyeon Gu,Yu-Jeong Jang,Ui Beom Park,Tae Jun Jeong,Hyun Tae Lee,허용석 한국구조생물학회 2022 Biodesign Vol.10 No.3
Cobolimab is an investigational antibody targeting Tim-3, an immune checkpoint protein associated with the suppression of T-cell response against cancer cells. This antibody’s safety and anti-tumor effectiveness were made clear in the clinical trial of the combination therapy using cobolimab and a PD-1 antibody. Here, the crystal structure of the cobolimab Fab in complex with an anti-kappa nanobody is determined. The crystals belonged to the space group C2221, with unit cell parameters a = 64.30, b = 119.30, and c = 184.49 Å. The structure was refined to a resolution of 2.02 Å with Rwork/Rfree = 0.197/0.233. The nanobody in the structure facilitated crystallization by restricting the elbow flexiblity of the Fab and providing extra packing interface for crystallization. This structure can be used as a model structure for predicting the protein-protein interaction between cobolimab and Tim-3.
Seung Beom Choi,Yu-Jeong Jang,Nahyeon Gu,Yong-Seok Heo 한국구조생물학회 2023 Biodesign Vol.11 No.4
Gemtuzumab ozogamicin is an antibody-drug conjugate consisting of a toxin chemically bound to an antibody that detects the CD33 protein on tumor cells. CD33 is a myeloid differentiation antigen displayed on acute myeloid leukemia (AML) blasts in most patients and has thus been highlighted as a potential target. When administrated to AML patients, gemtuzumab binds to CD33 and facilitates the uptake of the toxic payload into the cells, leading to cell death. Here, the crystal structure of the gemtuzumab Fab was determined to 2.50 Å resolution, with R/Rfree = 0.191/0.219. The five complementarity determining regions (CDRs) of gemtuzumab but the CDR1 of the heavy chain (HCDR1) are clearly displayed in the structure with apparent electron density. The results of this structural study may aid in predicting the binding mode of gemtuzumab to CD33, supporting the development of an ADC with increased therapeutic potency for the treatment of AML.