Humanized Immune Checkpoint Mouse Models

A beacon of hope for cancer treatment through daring innovation

GemPharmatech has developed a series of proprietary humanized mouse models targeting immune checkpoint molecules on both BALB/c and C57BL/6 genetic backgrounds. The extracellular regions of the mouse immune checkpoints are replaced with the corresponding human fragments, supporting antibody recognition against human immune checkpoints while ensuring proper intracellular signal transduction through the mouse transmembrane and intracellular portions. These models are suitable for antibody efficacy and safety evaluation including bispecific antibody evaluation for cancer immunotherapy and other applications. We provide comprehensive in vivo R&D testing services to our clients by offering appropriate solutions for disease models and study designs corresponding to their drug’s mechanism of action. We offer 60+ of these mouse models for a myriad of scientific applications. Our goal is to develop 600 humanized models for therapeutic development by the end of 2022.

 

Immune checkpoint molecules are a type of cell-surface proteins expressed on white blood cells or tumor cells. They act as a gatekeeper of immune responses by either activating or inhibiting signaling pathways upon ligand binding. Immune checkpoint antibodies target these proteins for efficient tumor removal. Breakthroughs in adaptive immune cell therapy (e.g., CAR-T, CAR-NK) and immunotherapies based on checkpoint biology (e.g., PD-1, CTLA-4 antibodies) represent a bright future for cancer treatment and bring hope for better patient care. Despite significant advances in the field, developing humanized immune checkpoint mouse models has emerged as one of the most difficult challenges for preclinical research and drug safety evaluation.

Models are available on dual genetic backgrounds


Single Target

Strain No.Strain NameStrain type
T003095B6-hPD1Knockin(KI),CRISPR/Cas9
T002726BALB/C-hPD1Knockin(KI),CRISPR/Cas9
T003455B6-hPDL1Knockin(KI),ES
T003260BALB/c-hPDL1Knockin(KI),ES
T003366B6-hTIGITKnockin(KI),CRISPR/Cas9
T003365BALB/c-hTIGITKnockin(KI),CRISPR/Cas9
T003362B6-hCTLA4Knockin(KI),CRISPR/Cas9
T003361BALB/c-hCTLA4Knockin(KI),CRISPR/Cas9
T003360B6-hCD137Knockin(KI),CRISPR/Cas9
T003359BALB/c-hCD137Knockin(KI),CRISPR/Cas9
T001550BALB/c-hCD3ETransgenic(Tg)
T009031BALB/c-hCD3EDGTransgenic(Tg)
T003597B6-hLAG3Knockin(KI),CRISPR/Cas9
T003894BALB/c-hTIM3Knockin(KI),ES
T004615B6-hSIRPαKnockin(KI),CRISPR/Cas9
T007666B6-hCD47Knockin(KI),CRISPR/Cas9
T014646BALB/c-hCD47Knockin(KI),CRISPR/Cas9
T002140B6-hOX40Knockin(KI),CRISPR/Cas9
T004363BALB/c-hOX40Knockin(KI),CRISPR/Cas9
T014695B6-hCD73Knockin(KI),CRISPR/Cas9
T006214B6-hFcRnKnockin(KI),CRISPR/Cas9
T014757BALB/c-hVISTRKnockin(KI),CRISPR/Cas9


Double Target

Strain No.Strain NameStrain type
T004022B6-hPD1/hPDL1Knockin(KI),CRISPR/Cas9,ES
T004025BALB/c-hPD1/hPDL1Knockin(KI),CRISPR/Cas9,ES
T004024B6-hPD1/hTIGITKnockin(KI),CRISPR/Cas9
T004023BALB/c-hPD1/hTIGITKnockin(KI),CRISPR/Cas9
T003826B6-hPD1/hCTLA4Knockin(KI),CRISPR/Cas9
T003720BALB/c-hPD1/hCTLA4Knockin(KI),CRISPR/Cas9
T004082B6-hPD1/hCD137Knockin(KI),CRISPR/Cas9
T004005BALB/c-hPD1/hCD137Knockin(KI),CRISPR/Cas9
T004621B6-hPD1/hLAG3Knockin(KI),CRISPR/Cas9
T004622BALB/c-hPD1/hLAG3Knockin(KI),CRISPR/Cas9
T004795BALB/c-hPD1/hTIM3Knockin(KI),CRISPR/Cas9
T009737B6-hPD1/hTIM3Knockin(KI),CRISPR/Cas9
T004279B6-hPD1/hCD28Knockin(KI),CRISPR/Cas9
T006778B6-hPD1/hCD27Knockin(KI),ES
T004081B6-hPD1/hBTLAKnockin(KI),CRISPR/Cas9
T004138BALB/c-hPD1/hBTLAKnockin(KI),CRISPR/Cas9,ES
T004061BALB/c-hPD1/hGITRKnockin(KI),CRISPR/Cas9
T006929B6-hSIRPα/hPD1Knockin(KI),CRISPR/Cas9
T004666B6-hPD1/hCD47Knockin(KI),CRISPR/Cas9
T037264BALB/c-hCD47/hSIRPαKnockin(KI),CRISPR/Cas9
T005313BALB/c-hPD1/hCD47Knockin(KI),CRISPR/Cas9
T003804BALB/c-hPD1/hOX40Knockin(KI),CRISPR/Cas9
T004421B6-hPD1/hOX40-v2Knockin(KI),CRISPR/Cas9
T003532B6-hPD1/hOX40Knockin(KI),CRISPR/Cas9
T006213B6-hPD1/hCSF1RKnockin(KI),CRISPR/Cas9


Multi Target

Strain No.Strain NameStrain type
T006873B6-hPD1/hPDL1/hTIGITKnockin(KI),CRISPR/Cas9,ES
T037004BALB/c-hPD1/hPDL1/hTIGITKnockin(KI),ES
T007058BALB/c-hPD1/hPDL1/hCTLA4Knockin(KI),CRISPR/Cas9,ES
T007056BALB/c-hPD1/hPDL1/hCD137Knockin(KI),CRISPR/Cas9,ES
T006876B6-hPD1/hPDL1/hLAG3Knockin(KI),CRISPR/Cas9,ES
T037005BALB/c-hPD1/hPDL1/hLAG3Knockin(KI),CRISPR/Cas9,ES
T007059BALB/c-hPD1/hPDL1/hTIM3Knockin(KI),CRISPR/Cas9,ES
T050194BALB/c-hPD1/hPDL1/hSIRPαKnockin(KI)
T009410B6-hPD1/hPDL1/hCD73Knockin(KI),CRISPR/Cas9
T036652BALB/c-hPD1/hPDL1/hCD73Knockin(KI),CRISPR/Cas9,ES


Advantages of GemPharmatech’s Humanized Immune Checkpoint Mouse Models:

  • Single, double, and triple knockin models of all known human immune checkpoint targets

  • Better simulation of the clinical side effects of immune checkpoint antibody drugs

  • Better suitability for evaluating combination therapy or comparing different drug candidates