HuGEMM™ CD3E Mouse Model

FATZO Mouse

cvmd-magnifyglass.png

HuGEMM™ CD3E Mouse Model Description

The HuGEMM CD3E mouse is a transgenic model where the CD3E chain of the CD3 co-receptor has been humanized for a more translational immune response.

The CD3E model was developed via insertion of an engineered BAC chromosome in a BALB/c background to express the human CD3ε gene, which allows the CD3E chain to be recognized by human specific immunotherapies. This enables the testing of therapeutic efficacy directly in the mouse model.

CD3E is one of four subunits of the CD3 co-receptor, which plays an important role in the immune response, associating with the T cell receptor (TCR) to couple antigen recognition to intracellular signal transduction, leading to T cell activation.

Benefits of the HuGEMM CD3E Model

  • Enables the in vivo evaluation of CD3E targeted, human-specific T cell engagers

  • Provides an efficient model to study a range of human origin bispecific antibodies

  • Transgene expression does not affect normal T cell development, unlike other previously developed models

  • Displays strong T cell activation post anti-CD3E stimulation, with consistent IL-2 and IFNγ secretion

CD3E Model Characterization Data

Figure 1 (data generated by the Nanjing Biomedical Research Institute of Nanjing University, NBRI-NJU): FACS analysis confirms human CD3E expression in HuGEMM CD3E transgenic mice, and that T cells co-express both human and mouse CD3E.

Figure 2 (data generated by the Nanjing Biomedical Research Institute of Nanjing University, NBRI-NJU): T cell stimulation assay demonstrates T cell activation following anti-CD3E administration, which can be induced by both anti-human and anti-mouse CD3E antibodies.

Figure 3: Validation of HuGEMM CD3E with bispecific CD3-CD20 antibodies. Tumor growth inhibition of the A20 model is observed following treatment with bispecific CD3-CD20 antibodies.