Preclinical Double-Humanized CTLA-4/LAG3 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hCTLA-4/hLAG3 mouse

The double-humanized CTLA-4 and LAG3 mouse model (hCTLA-4/hLAG3) was generated by intercrossing hCTLA-4 and hLAG3 mice.

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).

The hLAG3 humanized model, developed by Knockin at the mouse Lag3 locus, expresses the full length chimeric LAG3 isoform (human signal peptide, human extracellular domains, and mouse transmembrane and intracellular domains).

Both hCTLA-4 and hLAG3 expressions are regulated by endogenous mouse promoters.

Applications in immuno-oncology

The hCTLA-4/hLAG3 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint CTLA-4 and/or LAG3 in fully immunocompetent mice.

 

Request a quote here to get pricing, offers and hCTLA-4/hLAG3 model information by phone or email.

  

hCTLA-4/hLAG3 features and validation

The model has been developed and currently undergoes further validation steps by our partners of the precompetitive consortium – company leaders in immuno-oncology and immunotherapy.

Read more about the consolidation of the consortium with key industrial partners (including BMS, Charles River, Alligator, etc.) to validate humanized immune checkpoint mouse models. 

 

hCTLA-4 + hLAG3 ICP model validation 1

hCTLA‑4 expression pattern in hCTLA-4/hLAG3 mice recapitulates mCTLA-4 in wild-type mice

Splenocytes from hCTLA-4/hLAG3 double-homozygous mice were activated with coated αCD3/αCD28 and mIL-2 for 2 days (A, B) or indicated time (C,D). hCTLA-4 and mCTLA-4 expressions were evaluated on A) Tregs (viable, CD3+CD4+CD25+Foxp3+), B) conventional CD4+ (viable, CD3+CD4+Foxp3-), and C, D) CD8+ (viable, CD3+CD8+) T cells.

hCTLA-4 + LAG3 ICP model validation 2

hLAG3 expression pattern in hCTLA‑4/hLAG3 double-humanized model

Splenocytes from wild-type or hCTLA-4/hLAG3 double-homozygous mice were activated with coated αCD3/αCD28 and mIL-2 for 2 days (A, B) or indicated time (C, D). hLAG3 and mLAG3 expression on A) Tregs (viable, CD3+CD4+CD25+Foxp3+), B) conventional CD4+ (viable, CD3+CD4+Foxp3-), and C, D) CD8+ (viable, CD3+CD8+) T cells.

 

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

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