微信公众号

请长按图片识别二维码

模型资源

首页 模型资源 靶点人源化模型 hPD-1/hVISTA

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.

‍

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

  • hPD-1 expression pattern in hPD-1/hVISTA mice recapitulates mPD-1 in wild-type mice

    hPD-1 and mPD-1 expression on αCD3/αCD28-activated splenocytes on Tregs (A) and conventional CD4+ (B) at day 2 of culture, and on CD8+ T cells (C) at the indicated time points.

     

  • hVISTA expression pattern in hPD-1/hVISTA mice recapitulates mVISTA in wild-type mice

    hVISTA and mVISTA expression on freshly isolated splenocytes on Tregs, conventional CD4+, and CD8+ T cells.

Case studies

  1. Uncoupling efficacy from toxicity: a case study on MEDI5752

Commentaries

  1. VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response
  2. A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors
  3. CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity
  4. A new promising family of small molecules regulating the PD-L1/PD-1 signaling pathway
  5. A new Nature report by Bristol-Myers Squibb provides new insights into VISTA biology and design of combination therapies
  6. A VISTA on naive T cell fate
  7. An alternative approach to immunotherapy: A bispecific agonist 
     

Scientific articles

  1. A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors
  2. VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response
  3. Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells
  4. Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment
  5. VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance
  6. VISTA is an acidic pH-selective ligand for PSGL-1
  7. An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy
  8. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+Activated T Cells

Posters

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