Can't Use Syngeneics Due to Specificity Issues?
Evaluate your Human-Specific Agents In Vivo using our Unique Platforms of Humanized Drug Targets in Functional Murine Immune Systems
Checkpoint inhibitors such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 have revolutionized immunotherapy, and are now approved for a range of cancer types. Their preclinical evaluation is hindered, however, by a lack of available in vivo models for testing human-specific therapeutics. Surrogate anti-mouse checkpoint inhibitors were initially evaluated in syngeneic models, but these cannot be used for human biological therapeutics due to species specificity issues.
CrownBio has therefore developed HuGEMM, a valuable platform for clients to study a range of specific human biological therapies in vivo, in mice with a fully functional murine immune system featuring a humanized drug target e.g. with the murine target protein such as PD-1 directly replaced with its human counterpart.
HuGEMM Concept: PD-1 and CTLA-4 Models Available
Available HuGEMM Models
Other Available Models:
- CD137 and TIM3
- Homozygotes available
- PD-L1, LAG3, GITR, CD40, and double knock-ins
- Models under development for a range of other immuno-oncology targets.
Interested in Agents Targeting Proteins on Tumor Cells, e.g. PD-L1?
The sister platform to HuGEMM is HuCELL, which is used to evaluate the efficacy of agents targeting proteins expressed on tumor cells e.g. PD-L1.
CrownBio has engineered mouse tumor cells to express humanized ligands, with an MC38 model available expressing human PD-L1 for the evaluation of anti-human PD-L1 antibodies. HuCELL and HuGEMM models are combined as required to suit our client’s research needs.
The Concept and Genetic Engineering
Strategy of HuCELL
CRISPR/Cas9 gene editing is used to efficiently develop both model platforms, which are fully validated for human protein expression by FACS, as well as ligand and antibody binding.
Robust response to respective anti-human antibodies is observed for all of our validated models, with treatment data including anti-hPD-1, PD-L1, and CTLA-4 available for our HuGEMM and HuCELL platforms (and stored within MuBase®). Increased tumor infiltrating lymphocytes have been observed in our models, providing further validation and confidence in these unique platforms for immunotherapy evaluation.