Preclinical Double-Humanized PD-1/CTLA-4 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hPD‑1/hCTLA-4 mouse

The double-humanized PD-1 and CTLA-4 mouse model (hPD-1/hCTLA-4) was generated by intercrossing hPD-1 and hCTLA-4 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 hCTLA-4, developed by Knockin at the mouse CTLA-4 locus, enables the expression of: a) the full-length chimeric CTLA-4 isoform (human extracellular domain and mouse intracellular domain); and b) the soluble isoform (human extracellular domain).

Both hPD-1 and hCTLA-4 expressions are regulated by endogenous mouse promoters.

Applications in immuno-oncology

The hPD-1/hCTLA-4 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint PD-1 and/or CTLA-4 in fully immunocompetent mice.

Humanized tumor cell line MC38-hPD-L1:
Use our hPD-1/hCTLA-4 mouse model together with our cell line MC38-hPD-L1 as a syngeneic tumor model for testing the efficacy of combination therapies targeting human PD-1 and human PD-L1.

 

Request a quote here to get pricing, offers and hPD-1/hCTLA-4 model information by phone or email.

  

hPD-1/hCTLA-4 features

  • The PD-1 and CTLA-4 extracellular domains are entirely humanized
  • Physiological regulation and expression pattern of the human PD-1 and CTLA-4
  • 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/hCTLA-4 validation*

The model has been co-validated by partners of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.

Publication with the model by Oncology R&D, AstraZeneca in January 2021:
Simon J Dovedi, et al. Design and efficacy of a monovalent bispecific PD-1/CTLA-4 antibody that enhances CTLA-4 blockade on PD-1+ activated T cells. Cancer Discov. 2021 Jan 8

hPD-1+hCTLA-4 ICP model validation 1

hPD-1 and hCTLA-4 expression patterns in hPD-1/hCTLA-4 mice recapitulate mPD-1 and mCTLA-4 in wild-type mice

Splenocytes from hPD-1/hCTLA-4 double homozygous mice were activated with αCD3/αCD29. Expressions of hPD-1 and mPD-1 (upper panel), and hCTLA and mCTLA-4 (lower panel) were evaluated on conventional CD4 (viable, CD3+CD4+Foxp3-) T cells at indicated time points.

hPD-1+hCTLA-4 ICP model validation 2

hPD-1 and hCTLA-4 are expressed on TILs (tumor-infiltrating lymphocytes)

PD-1 and CTLA-4 expression on TILs from mice bearing MCA205 tumors. Mouse and human PD-1 and CTLA-4 expression were analyzed on wild-type and hPD-1/hCTLA-4 homozygous mice.

* For more validation data please consult our hPD-1 and hCTLA-4 webpages, or  contact us.

 

Further reading

 

Ready to be shipped to your lab

  • Cohorts available upon request
  • Studies can be carried out at your site or at your favorite CRO
  • SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation

Are you looking for another target?
Follow this link for humanized immune checkpoint (ICP) mouse models, or contact us.