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 DOI: 10.2210/pdb8tbq/pdb
• Descriptor: SNS-101 Fab heavy chain, SNS-101 Fab light chain, V-type immunoglobulin domain-containing suppressor of T-cell activation, ... (6 entities in total)
• Functional Keywords: vista, ph-selective, sns-101, pd-1, protein binding, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 132211.84

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 citation

Thisted, 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

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

Experimental method

X-RAY DIFFRACTION (2.593 Å)