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hPD-1/hVISTA
Humanized mice (target-specific)

Preclinical double-humanized PD-1/VISTA mouse model

The hPD-1/hVISTA mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint PD-1 and/or VISTA in fully immunocompetent mice.

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Design of the hPD‑1/hVISTA mouse

The double-humanized PD-1 and VISTA mouse model (hPD-1/hVISTA) was generated by intercrossing hPD-1 and hVISTA mice.

hPD-1 has been developed by inserting, within the mouse PD-1 locus, a chimeric PD-1 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain. hVISTA has been developed by inserting, within the mouse VISTA locus, a chimeric VISTA with a human extracellular, human transmembrane and murine intracellular domain.

Both hPD-1 and hVISTA expressions are regulated by endogenous mouse promoters.

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hPD-1/hVISTA features

  • The PD-1 and VISTA extracellular domains are entirely humanized
  • Physiological regulation and expression pattern of the human PD-1 and VISTA
  • Preservation of the target-ligand interaction
  • Fully functional mouse immune system
  • Lack of expression of the murine target gene, thus avoiding cross-reactivity

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PosterS
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Scientific Articles
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(Cidara) Discovery of a multispecific CD73/PD-1 targeting Drug Fc-Conjugate (DFC), which improves tumor reduction compared to PD-1 monotherapy in a humanized mouse model

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(Reaction Biology) Humanized PD-1 knock-in mice as a model system for combination therapies with human specific PD-1 therapeutics

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Anti-VISTA agents profiling: complementarity of BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies

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(Sensei) SNS-101, a monoclonal antibody that is highly selective for VISTA in the tumor microenvironment, demonstrates favorable pharmacokinetic and cytokine release characteristics and potentiates anti-PD-1 responsiveness

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(Kineta) A Fully Human anti-VISTA Antibody as a Promising Therapy Against Poorly Immunogenic Tumors

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(Charles River) Novel in vivo preclinical humanized models for the evaluation of human specific immune checkpoint inhibitors.

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Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993

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

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

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Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells

J Allergy Clin Immunol

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An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy

Nat Cancer

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Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment

J Immunother Cancer

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Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1 + Activated T Cells

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VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

Science

Jan 2020
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VISTA is an acidic pH-selective ligand for PSGL-1

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