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8TBQ

The crystal structure of human VISTA extra cellular domain in complex with Fab fragment of pH-selective anti-VISTA antibody

Summary for 8TBQ
Entry DOI10.2210/pdb8tbq/pdb
DescriptorSNS-101 Fab heavy chain, SNS-101 Fab light chain, V-type immunoglobulin domain-containing suppressor of T-cell activation, ... (6 entities in total)
Functional Keywordsvista, ph-selective, sns-101, pd-1, protein binding, immune system
Biological sourceHomo sapiens
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Total number of polymer chains6
Total formula weight132211.84
Authors
van der Horst, E.H.,Mukherjee, A.,Thisted, T. (deposition date: 2023-06-29, release date: 2024-03-20, Last modification date: 2024-10-16)
Primary citationThisted, T.,Smith, F.D.,Mukherjee, A.,Kleschenko, Y.,Feng, F.,Jiang, Z.G.,Eitas, T.,Malhotra, K.,Biesova, Z.,Onumajuru, A.,Finley, F.,Cifuentes, A.,Zhang, G.,Martin, G.H.,Takeuchi, Y.,Thiam, K.,Schreiber, R.D.,van der Horst, E.H.
VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response.
Nat Commun, 15:2917-2917, 2024
Cited by
PubMed Abstract: VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens.
PubMed: 38575562
DOI: 10.1038/s41467-024-47256-x
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.593 Å)
Structure validation

227344

건을2024-11-13부터공개중

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