Preclinical Humanized CTLA-4 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hCTLA-4 mouse

The humanized CTLA‑4 mouse model (hCTLA-4) is developed by Knockin at the mouse CTLA‑4 locus, and enables the expression of: a) the full-length chimeric CTLA-4 isoform; and b) the soluble isoform.

The design also gives access to CTLA-4 conditional Knockout mice for a tissue-specific assessment of compounds’ specificity and toxicity.

Applications in immuno-oncology

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

Access to conditional CTLA-4 Knockout mouse:
The conditional Knockout model allows the tissue-specific assessment of compounds’ specificity and toxicity.

See also:

 

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

 

hCTLA-4 features

  • The CTLA-4 extracellular domain is entirely humanized
  • Physiological regulation and expression pattern of the human 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

hCTLA-4 validation*

The model has been co-validated by Charles River, our partner of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.

A scientific poster was presented at the Tumour Models 2019 in London. Download poster

hCTLA-4 ICP model validation 1

hCTLA-4 expression pattern recapitulates mCTLA-4

hCTLA-4 and mCTLA-4 expression on αCD3-activated splenocytes on A) Tregs (viable, CD3+CD4+CD25+Foxp3+), B) conventional CD4+ (viable, CD3+CD4+Foxp3-) at day 3, and C) CD8+ (viable, CD3+CD8+) T cells at indicated time points.

hCTLA-4 ICP model validation 2

In vivo anti-tumor activity is observed in response to ipilimumab in hCTLA‑4 mice

Wild-type and hCTLA-4 mice were implanted s.c. with MC38 tumor on day 0 with n=10 mice per group. Survival of mice treated with αhCTLA-4 (ipilimumab), αmCTLA-4 (9H10) or isotype i.p. bi-weekly for 2 weeks.
(Mantel-Cox test: ****p<0.0001)

* For more validation data please contact us.

Ready to be shipped to your lab

  • Cohorts available upon request
  • Studies can be carried out at your site or at your favorite CRO
  • VAF Elite/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 humanized immune checkpoint (ICP) mouse models, or contact us.