HuGEMM™ CTLA-4 Mouse Model

FATZO Mouse

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HuGEMM™ CTLA-4 Mouse Model Description

The HuGEMM CTLA-4 mouse model is a chimeric tumor model where the mouse immune system is functional and the CTLA-4 receptors have been humanized for a more translational immune response.

The CTLA-4 model was developed by replacing mouse exons 2 and 3 with their human counterparts (murine exons 1 and 4 remain). This allows the receptor to be recognized by therapeutic antibodies of interest, and enables the ability to test the therapeutic efficacy directly in the mouse model.

CTLA-4 plays an important role in the immune response, acting as an immune checkpoint, downregulating T cell function, and inhibiting excessive expansion of activated T cells.

Benefits of HuGEMM Models

  • Humanized drug targets eliminate and reduce interspecific (species) effects of the compound providing a platform to evaluate therapeutic antibodies which are not cross-reactive to the mouse protein

  • Enables the evaluation of specific human biological therapies in vivo when no mouse ortholog is available

  • Provides an efficient method to study a range of targets for human immunotherapies

CTLA-4 Model Characterization Data

Figure 1: FACS analysis confirms that HuGEMM CTLA-4 knock in models express human CTLA-4 on T cells.

Figure 2: Validation of HuGEMM CTLA-4 with an ipilimumab analog. Tumor growth inhibition of the MC38 model is observed following treatment with the anti-hCTLA-4 antibody.