humanized mice to study FcγR function.

Area of Science:

• Immunology
• Pharmacology
• Preclinical Research

Background:

• Passive immunotherapy using monoclonal antibodies is vital for treating neoplastic, inflammatory, and infectious diseases.
• Fc-mediated effector functions significantly influence antibody activity in vivo, necessitating their thorough understanding for therapeutic development.
• Existing animal models (murine, non-human primate) exhibit FcγR variations, limiting their utility in predicting human therapeutic antibody efficacy.

Purpose of the Study:

• To develop and evaluate an Fc receptor-humanized mouse model for studying human FcγR function in vivo.
• To enable accurate preclinical assessment of therapeutic antibodies targeting human FcγR interactions.

Main Methods:

• Development of a genetically engineered mouse model with deleted endogenous mouse FcγR genes.
• Introduction of human FcγRs as transgenes, ensuring faithful recapitulation of human FcγR expression patterns.
• Evaluation of cytotoxic and therapeutic antibody activities in vivo using the FcγR-humanized mice.

Main Results:

• The FcγR-humanized mouse model accurately reflects human FcγR expression and function.
• In vivo evaluation of antibodies in this model provided significant insights into human IgG Fc effector functions.
• The model demonstrated utility in assessing antibodies for treating malignancies, autoimmunity, inflammation, and infectious diseases.

Conclusions:

• Fc receptor-humanized mice are a crucial preclinical tool for evaluating human therapeutic antibodies.
• This model overcomes limitations of traditional animal models, offering more relevant data on FcγR-mediated antibody activities.
• The developed model is vital for advancing the efficacy of antibody-based therapies across various diseases.