Preclinical humanized VISTA mouse model
The hVISTA mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint VISTA in fully immunocompetent mice.
Design of the hVISTA mouse
The humanized VISTA mouse model (hVISTA) is developed by Knockin at the mouse VISTA locus, and expresses a chimeric VISTA with a human extracellular, human transmembrane and murine intracellular domain.
The design also gives access to VISTA conditional Knockout mice for a tissue-specific assessment of compounds’ specificity and toxicity.
hVISTA features
- The VISTA extracellular domain is entirely humanized
- Physiological regulation and expression pattern of the human VISTA
- Fully functional mouse immune system
- Lack of expression of the murine target gene, thus avoiding cross-reactivity
Validation
hVISTA expression pattern recapitulates mVISTA
hVISTA and mVISTA expression on freshly isolated splenocytes on A) Tregs, B) CD11bHigh, C) conventional CD4 (CD4conv), and D) CD8 T cells. VISTA is not detected on cells from VISTA Knockout homozygous mice.
Anti-tumor effects in response to anti-human VISTA + anti-mouse PD-1 treatment
Mice of indicated genotype were inoculated with MC38 tumor cells s.c. and treated αKLH (control), αmPD-1, αhVISTA or αmPD-1 + αhVISTA (combination). Tumor volume measurement in A) wild-type and B) hVISTA Knockin (KI) homozygous mice at different time points. Results are expressed as mean±SEM. C) Survival of treated hVISTA KI homozygous mice analyzed up to 50 days post MC38 tumor inoculation.
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Preclinical humanized VISTA mouse model
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