Humanized Animal Models for Advanced Antibody Production

University of Pittsburgh researchers have developed a novel animal model that uses humanized animals to produce human monoclonal antibodies. This model involves reconstituting human immune cells, spleen, and thymus in severely immunodeficient mice, along with co-engrafting autologous full-thickness human skin. This innovative approach aims to overcome the limitations of current monoclonal antibody therapies, which are developed using the murine immune system and can lead to adverse immune reactions in humans. The new model enables the development of robust human monoclonal antibodies under the control of human immune system signaling, significantly reducing immunogenicity and increasing efficacy.

Description

The technology involves creating a humanized animal model by reconstituting human immune cells, spleen, and thymus in severely immunodeficient mice, and co-engrafting autologous full-thickness human skin. This model shows high levels of human immune cell repopulation and robust human IgG levels. The human spleen in these animals develops lymphoid follicles and germinal centers, which are crucial for antibody-producing B cells. The human skin can be vaccinated with desired antigens via DNA or protein delivery, eliciting robust antibody production. Antibody-producing B cells are then isolated and fused to human hybridoma partner cells to generate monoclonal antibodies.

Applications

- Production of human monoclonal antibodies
- Evaluation of vaccines, immunotherapies, and drugs
- Research on human immune system responses
- Development of treatments for diseases such as HIV, EBV, and Dengue

Advantages

This technology offers a novel approach to producing human monoclonal antibodies using human immune system signaling, which reduces immunogenicity and increases efficacy. The model allows for the development of antibodies through various vaccination strategies, including human skin vaccination, intraperitoneal, and intravenous methods. Additionally, it enables the evaluation of vaccines and immunotherapies in a humanized system, providing more accurate insights into their effects on the human immune system.

Invention Readiness

The technology is currently at the in vivo data stage, with several key experimental steps completed. Researchers have successfully reconstituted human immune cells, spleen, and thymus in severely immunodeficient mice, and co-engrafted autologous full-thickness human skin. Analysis of the blood in these animals shows high levels of human immune cell repopulation and robust human IgG levels. The human spleen in these animals develops lymphoid follicles and germinal centers, essential for antibody-producing B cells.

IP Status

Research Tool