A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors

Shawn Iadonato
Kineta, Inc.
October 31, 2023
Front Immunol
https://pubmed.ncbi.nlm.nih.gov/38152397

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

https://pubmed.ncbi.nlm.nih.gov/38152397

Research summary

This study reports the development and characterization of KVA12123, a fully human monoclonal antibody targeting VISTA (V-domain Ig suppressor of T cell activation), an immune checkpoint molecule predominantly expressed on myeloid cells. The research evaluates KVA12123's binding specificity, mechanism of action, antitumor efficacy, and safety profile, highlighting its potential as a novel immunotherapy for cancers with low immunogenicity.

Key outcome of the study

KVA12123 demonstrated high-affinity binding to human VISTA, effectively blocking its interaction with known ligands. In vivo studies using the hVISTA-KI mouse model showed that KVA12123 treatment led to significant tumor growth inhibition in multiple syngeneic tumor models, both as a monotherapy and in combination with anti-PD-1 therapy. The antibody was well-tolerated in preclinical safety studies, with no significant toxicity observed.

Mouse model

The study utilized a human VISTA Knockin (hVISTA-KI) mouse model developed by genOway. In this model, the extracellular domain of murine VISTA was replaced with the human counterpart, enabling the assessment of KVA12123's efficacy and mechanism of action in a physiologically relevant setting.

TARGET:
VISTA
VSIR, PD-1H, B7-H5

Keywords

Immuno-oncology, Immune checkpoint inhibition, VISTA, Monoclonal antibody therapy, Tumor immunogenicity

Technical specifications

Humanized Knockin mouse model, VISTA targeting, Antibody development, Syngeneic tumor models, Preclinical safety assessment

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Catalogue product

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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