A novel mouse strain optimized for chronic human antibody administration

Area of Science:

• Immunology
• Pharmacology
• Oncology

Background:

• Therapeutic human IgG antibodies are crucial for treating various diseases.
• Assessing long-term efficacy and safety is hindered by mouse anti-human IgG immune responses.
• Current mouse models limit the duration and dosage of human antibody treatments.

Purpose of the Study:

• To develop a mouse model tolerant of chronic human antibody administration.
• To enable long-term in vivo testing of human monoclonal antibodies.
• To overcome limitations in evaluating antibody therapeutics in preclinical models.

Main Methods:

• Development of a mouse model with human IgG1 heavy chain knock-in.
• Full recapitulation of human Fc receptor (FcγR) expression in the model.
• Testing the model in chronic models of immune thrombocytopenic purpura and metastatic melanoma.

Main Results:

• The developed mouse model exhibits minimal anti-human IgG responses.
• Sustained persistence of therapeutically active human IgG was observed.
• The model allows for extended duration and dosing of human antibody treatments.

Conclusions:

• This novel mouse model provides a unique platform for chronic in vivo testing of human monoclonal antibodies.
• It overcomes limitations of previous models, allowing for more accurate preclinical assessment of antibody therapeutics.
• The model facilitates better evaluation of long-term efficacy and safety in various disease contexts.