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.
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.
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.
Immuno-oncology, Immune checkpoint inhibition, VISTA, Monoclonal antibody therapy, Tumor immunogenicity
Humanized Knockin mouse model, VISTA targeting, Antibody development, Syngeneic tumor models, Preclinical safety assessment
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