Immunocompromised Human Serum Albumin/Human Neonatal Fc Receptor Mouse Model

Humanized Immune Checkpoint Mouse Models

Our double-humanized serum albumin/neonatal Fc receptor mouse model (HSA/hFcRn) maintains an autologous receptor-ligand interaction and can mimic the physiological drug clearance in humans.

This upgraded, immunocompromised Rag1-/- system (HSA/hFcRn/Rag1-/-) allows the assessment of compounds' half-life and anti-tumor efficacy in a human tumor model.

Applications

  • Efficacy assessment of drug conjugates, antibodies (e.g., T-cell engagers), and any albumin- and FcRn-binding compounds
  • Accurate and predictive PK/PD studies of albumin- and FcRn-binding compounds
 

Request a quote to get pricing, offers and HSA/hFcRn/Rag1-/- model information by phone or email.

 

HSA/hFcRn/Rag1-/- model features

  • Murine Rag1 is invalidated, leading to a deficiency in T- and B-cell development
  • Physiological HSA and hFcRn expression profile and regulation in a mouse system, as they are both controlled by their respective endogenous mouse promoters (murine albumin and FcRn expression is abolished)
  • Efficient tumor growth upon human cancer cells injection

HSA/hFcRn/Rag1-/- model validation

HSA/hFcRn/Rag1KO model validation 1

CD3+ T-cell and CD19+ B-cell development is abolished in HSA/hFcRn/Rag1-/- mice

Hemocytometer (A) and flow cytometry count of B and T cells in the thymus (B) and spleen (C) of wild-type (WT) and HSA/hFcRn/Rag1-/- (tHO) mice.

HSA/hFcRn/Rag1KO ICP model validation 2

Humanization of serum albumin and FcRn does not affect tumor growth in HSA/hFcRn/Rag1-/- mice

C57BL6 Rag1-/- (C57BL6 Rag1 KO) and HSA/hFcRn/Rag1-/- (AlbuMus RAG1 KO) mice were subcutaneously inoculated with HT-29 cells (colorectal cancer cells).
Original figure from Mandrup et al., Comm Biol 2021

HSA/hFcRn/Rag1KO model validation 3

Compound efficacy assessment in human breast and pancreatic cancer-cell xenografts

HSA/hFcRn/Rag1-/- mice were subcutaneously inoculated with MDA-MB-231 (left) or MIA PaCa-2 (right) cells. Mice were randomized and treated either with vehicle or with an albumin-bound drug once a week for 4 weeks, when individual tumor reached 250mm3.

* For more validation data please contact us.

 

Reference

Ole A Mandrup, Sui Ching Ong, Simon Lykkemark, Anders Dinesen, Imke Rudnik-Jansen, Niels Frederik Dagnæs-Hansen, Jan Terje Andersen, Luis Alvarez-Vallina, Kenneth A Howard.
Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity.
Commun Biol. 2021 Mar 8

 

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