6XKR

Structure of Sasanlimab Fab in complex with PD-1

6XKR の概要

• エントリーDOI: 10.2210/pdb6xkr/pdb
• 分子名称: Sasanlimab Fab Heavy chain, Sasanlimab Fab Light chain, Programmed cell death protein 1, ... (5 entities in total)
• 機能のキーワード: anti-pd-1, fab, complex, immuno-oncology, antitumor protein, antitumor protein-immune system complex, antitumor protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65490.76

構造登録者

Kimberlin, C.R.,Chin, S.M. (登録日: 2020-06-27, 公開日: 2020-09-09, 最終更新日: 2024-10-30)

主引用文献

Al-Khami, A.A.,Youssef, S.,Abdiche, Y.,Nguyen, H.,Chou, J.,Kimberlin, C.R.,Chin, S.M.,Kamperschroer, C.,Jessen, B.,Kern, B.,Budimir, N.,Dillon, C.P.,Xu, A.,Clark, J.D.,Chou, J.,Kraynov, E.,Rajpal, A.,Lin, J.C.,Salek-Ardakani, S.
Pharmacologic Properties and Preclinical Activity of Sasanlimab, A High-affinity Engineered Anti-Human PD-1 Antibody.
Mol.Cancer Ther., 19:2105-2116, 2020

PubMed Abstract: Development of antagonistic mAbs that specifically target the immune checkpoint receptor, programmed cell death protein-1 (PD-1), is of great interest for cancer immunotherapy. Here, we report the biophysical characteristics and nonclinical antagonistic activities of sasanlimab (PF-06801591), a humanized anti-PD-1 antibody of IgG4 isotype. We show that sasanlimab binds selectively and with similar high potency to human and cynomolgus monkey PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, with no detectable Fc-dependent effector function. The binding of sasanlimab to human and cynomolgus PD-1 is associated with the formation of a stable complex, which is likely to be the main driver of this high-affinity interaction. , sasanlimab significantly augmented T-cell proliferation and cytokine production in mixed lymphocyte reaction and superantigen stimulation assays. , sasanlimab accelerated the incidence of GvHD by enhancing T-cell proliferation and cytokine secretion in a xenogeneic model of acute GvHD and halted the growth of MC-38 colon adenocarcinoma tumors in human PD-1 knock-in mice. Pharmacokinetic and toxicokinetic findings from cynomolgus monkey showed that sasanlimab was active and well-tolerated. Taken together, the data presented here support the clinical development of sasanlimab for the treatment of patients with advanced cancers as a single agent or in combination with other immunotherapies.

PubMed: 32847983
DOI: 10.1158/1535-7163.MCT-20-0093

実験手法

X-RAY DIFFRACTION (2.59 Å)