VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

Thomas Thisted
Sensei Biotherapeutics
April 4, 2024
Nat Commun
https://pubmed.ncbi.nlm.nih.gov/38575562/

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/38575562/

Research summary

This study evaluates the efficacy and safety of SNS-101, a pH-selective antibody targeting the V-domain Ig suppressor of T cell activation (VISTA), in enhancing anti-PD-1 therapy responses. The research investigates how SNS-101 modulates immune checkpoints to improve cancer immunotherapy outcomes.

Key outcome of the study

SNS-101 demonstrated favorable pharmacokinetics and safety profiles, effectively enhancing the response to PD-1 blockade in tumor models. The combination therapy led to significant tumor growth inhibition, suggesting that pH-selective VISTA inhibition can potentiate anti-PD-1 immunotherapy.

Model

The study utilized human VISTA Knockin and BRGSF-HIS mouse models developed in collaboration with genOway. These models express human VISTA, allowing for the assessment of SNS-101's efficacy and safety in a humanized immune system context.

TARGET:
Vsir
Synonyms:
VISTA, C10orf54, PD-1H

Keywords

Cancer immunotherapy, Immune checkpoint inhibition, VISTA targeting, PD-1 blockade, Tumor immunology

Technical specifications

Humanized Knockin model, BRGSF-HIS mouse model, pH-selective antibody, Immune checkpoint modulation, Combination therapy evaluation

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genO‑hVISTA

The genO‑hVISTA mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint VISTA in fully immunocompetent mice.

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