Humanized Soluble Molecules

Model for Targets and Biomarkers

Secreted proteins are important targets and biomarkers for biomedical research. Humanization of these soluble molecules provide very valuable research models, such as the humanization of:

  • Immunoglobulin genes for the in vivo development of chimeric and fully human antibodies.
  • Transport proteins like albumin to study the impact of blood transport on the compound half-life or activity.
  • Interleukins and hormones for in vivo studies of NCE or antibodies targeting these soluble molecules.

Humanized models can also be used to generate models tolerant to a given human antibody isotype and avoid a mouse immune response against therapeutics antibody when tested in mice.

 

Case study: Generation of humanized IgG1 model for in vivo assessment of therapeutic humanized IgG1 efficacy and the toxicity.


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Humanized IgG1

The constant regions of both light and heavy chain of IgG1 immunoglobulins were humanized (red boxes).

Variable regions are of mouse origin.

 

 

Humanized IgG1 expression in mice

Humanized IgG1 Model is Fully Functional for Antibody Development and Testing

Upon stimulation, humanized IgG1 mice are producing human IgG1 and no mouse IgG1. The expression of other isotopes is unchanged. These mice are tolerant to human IgG1.

Humoral response was assessed by ELISA after stimulation with KLH. Mouse IgG1 immunoglobulins are not expressed. Human IgG1 is detected at standard level.

The model is producing all other mouse isotopes including IgM, IgD, IgG3, Ig2a, Ig2b, IgE, IgA (data not shown).