9W43
Structure of the complex of human PD-1 and a PD-1-directed antibody
Summary for 9W43
| Entry DOI | 10.2210/pdb9w43/pdb |
| EMDB information | 65617 |
| Descriptor | Heavy chain of 1C4 Fab fragment, Light chain of 1C4 Fab fragment, Programmed cell death protein 1 (3 entities in total) |
| Functional Keywords | pd-1, pd-1-directed antibody, antigen-antibody complex, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 58939.81 |
| Authors | |
| Primary citation | Jiang, W.,Li, L.,Xue, W.,He, X.,Chu, X.,Song, L.,Li, X.,Zhao, R.,Yuan, X.,Jin, X.,Fan, L.,Sun, T.,Zhu, A.,Zhou, L.,Gu, F.,Xu, Q.,Ma, G.,Wang, S.,Jin, L.,Xu, J.L. Dual agonism and selective T-cell depletion activity of a PD-1-directed antibody for treating autoimmune diseases. Mabs, 18:2624881-2624881, 2026 Cited by PubMed Abstract: Precise inhibition of autoreactivity without concomitant induction of general immunosuppression is an overarching goal that remains elusive for the treatment of autoimmune diseases. PD-1 is preferentially expressed on activated T cells that drive autoimmunity. These PD-1 T cells could serve as a target for therapeutic intervention. Here, we report the discovery of a unique PD-1 agonist antibody, GenSci120, that exhibited potent and selective T-cell inhibition in vitro and T-cell depletion activity both in vitro and in vivo. Target engagement by GenSci120 directly promoted SHP2 recruitment into the PD-1 signaling pathway but also enhanced the binding of PD-1 to its natural ligands and augmented PD-L1-induced PD-1 signaling. Moreover, GenSci120 exhibited robust efficacy in several animal models of human autoimmune disease. Thus, GenSci120, by selectively depleting PD-1 T cells and by directly (via PD-1 binding and SHP2 recruitment) or indirectly (via enhancing PD-1 and ligand interaction) stimulating PD-1 signaling, has the capability to restore immune balance in autoimmunity. In a first-in-human study in healthy adults (NCT06827457), GenSci120 demonstrated favorable safety/tolerability and pharmacokinetic profiles as well as robust pharmacodynamic effect. Together, these findings suggest the potential of GenSci120 as an innovative precision medicine for treating autoimmune diseases and support further evaluation of this investigational new drug in future clinical trials. PubMed: 41640111DOI: 10.1080/19420862.2026.2624881 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.96 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
