Immunocompromised double-humanized HSA/hFcRn-Rag1-KO mouse model
This upgraded, immunocompromised Rag1-/- version of our HSA/hFcRn mouse model allows the assessment of compounds' half-life and anti-tumor efficacy in a human tumor model.
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
HSA/hFcRn-Rag1-/- model features
- Murine Rag1 is invalidated, leading to a deficiency in T- and B-celldevelopment
- 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
Validation
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.
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 2021Compound 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.
Immunocompromised double-humanized HSA/hFcRn-Rag1-KO mouse model
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