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/hTIM3

Design of the hPD‑1/hTIM3 mouse

The double-humanized PD-1 and TIM3 mouse model (hPD-1/hTIM3) was generated by intercrossing hPD-1 and hTIM3 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.

The design of the TIM3 humanized model, developed by Knockin at the mouse TIM3 locus, enables the expression of a chimeric TIM3 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain.

‍

hPD-1/hTIM3 features

  • The PD-1 and TIM3 extracellular domains are entirely humanized
  • 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 and hTIM3 expression on tumor-infiltrated CD8 T cells

    Human TIM3 and human PD-1 expression on CD8 T cells isolated from tumor. Tumors were harvested 28 days post inoculation of MC38 cells in hPD-1/hTIM3 mice. Isolated cells were pre-gated on lymphocytes, single cells, living cells, CD45+/TCRβ+, and CD8+.

     

  • Anti-human TIM3 therapy in combination with anti-human PD-1 improves tumor protection when compared to vehicle or blocking PD-1 only.

    Survival of hPD-1/hTIM3 mice implanted subcutaneally with MC38 cells and treated with vehicle, αhPD-1, or αhPD-1 + αhTIM3 (two-way ANOVA; ****p<0.0001; ns: non-significant).

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. CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity
  3. A new promising family of small molecules regulating the PD-L1/PD-1 signaling pathway
  4. An alternative approach to immunotherapy: A bispecific agonist

Scientific articles

  1. An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy 
  2. Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells
  3. Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment
  4. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+Activated T Cells