Several partners have extensively co-validated the genO-hFcγR mouse model
Ex vivo ADCC induction by NK cells
- The humanized genO-hFcγR model is highly effective for evaluating human therapeutic antibodies, eliminating the need to test mouse-specific antibodies first. This is illustrated by the higher levels of NK cell-mediated ADCC observed in genO-hFcγR NK cells compared to NK cells from WT mice after anti-CD20 therapeutic antibody (RIX) treatment (graph A below). RIX is a monoclonal antibody with a regular hIgG1 Fc which targets CD20 on B cells, leading to their depletion.
- The genO-hFcγR model also allows for the translational assessment and ranking of human antibodies that induce ADCC. This is shown by the increased cell lysis following treatment with another anti-CD20 monoclonal antibody (Obinu.), which has been engineered to display enhanced Fc binding, relative to RIX (graph B below). This data reproduces what is observed in the clinic and confirms the effective hFcγRIII-mediated cytotoxicity, as well as the relevance of the genO-hFcγR model for immuno-oncology.
▶ Data on ADCC was presented at AACR 2024, courtesy of Ariane Morel, Caroline Denis and Rachel Courtois at Innate Pharma
.png)
In vivo Fc-dependent B-cell depletion
- An anti-CD20 antibody depleted B cells in the humanized genO-hFcγR model, while its silenced Fc variant did not. Antibody-mediated B-cell depletion is a powerful tool for treating autoimmune diseases and certain types of cancer such as B-cell lymphomas and leukemias.
▶ Similar data was presented at different conferences by us and argenx
Fc-dependent effect of anti-influenza A therapeutic antibodies
- The genO-hFcγR mice are susceptible to influenza A infection, as shown by the body weight loss in the absence of treatment (PBS). The anti-influenza antibody with enhanced Fc binding (anti-flu-GA) provides better prophylactic protection than the WT antibody or the Fc-null variant (anti-flu-GRLR) in genO-hFcγR mice. This shows that this model is also useful for studying infectious diseases and their therapies.
▶ For more details, see our poster presented at AACR 2024
What sets the genO-hFcγR model apart?
Our model presents unique features:
- Fully functional humanized receptors (FcγRI, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB) assessed in various immune cells including NK cells, T cells, and basophils.
- Human-like expression pattern of hFcγR that mirrors human FcγR diversity and distribution.
- No expression of murine FcγR
- Extensive dataset package generated with biopharma partners:
- Efficacy assessment of lead marketed ADCC-inducing antibodies (Rituximab & Obinutuzumab)
- Possibility to rank Fc-engineered antibodies
- Fc-dependent B-cell depletion induced by Fc-engineered anti-CD20 antibodies
Upgrades
In order to expand the range of applications of our genO-hFcγR mouse, it has been intercrossed with several other models:
EFFICACTY &SAFETY:
Assessment of T cell-targeting therapies:
- genO-panhCD3/hFcγR
- genO-hVISTA/hFcγR
- genO-hCCR8/hCCL1/hFcγR
- genO-hCTLA-4/hFcγR
Assessment of myeloid-targeting therapies:
- genO-hCD47/hSIRPα/hFcγR
TOLERANCE:
Increased tolerance to human IgG1:
- genO-hFcγR/hIgG1
PK:
Improved PK assessment of compounds with extended half-life:
- genO-hFcγR/hFcRn
BIODISTRIBUTION:
Improved biodistribution of compounds through the BBB
- genO-hTFRC/hFcγR
Humanized genO-hFcγR mouse for outstanding translatability
Get in touch about
Let us know how we can help
Scientific excellence
From model design to experimental results
Featured in 600+ scientific articles
Collaborative approach
Collaboration with 17 Top Pharmas,
170+ Biotechs and 380+ Academic Institutions
Robust validation data on catalog models
Generated with biopharma partners and in-house
Innovative technologies
and guaranteed freedom to operate
Easy access to models
Models with certified health status from professional breeders in US and Europe