Mingkun Zhang, Vice President at GemPharmatech focused on the application of animal models in antibody discovery. He contextualised the field by highlighting the significant advancements and challenges and he began by discussing the use of transgenic mice, particularly emphasizing their role in antibody discovery.
Transgenic mice, such as the Neomab platform, offer substantial benefits by incorporating human genes directly into the mouse genome. This approach eliminates the need for the humanization step, thereby saving time and money while reducing the risks associated with immunogenicity. The Neomab platform, specifically, is designed to produce fully human antibodies, which are crucial for therapeutic applications.
Zhang then addressed the various challenges faced in the development of antibody drugs. These challenges include target selection, protein engineering, and the complexity of the CMC (Chemistry, Manufacturing, and Controls) process.
One of the most significant hurdles is predicting immunogenicity risk during preclinical studies. Zhang provided an example of a drug that failed in phase III clinical trials due to immunogenicity issues. This reiterates the importance of addressing this challenge early in the development process.
The introduction of the NeoMab platform is a transgenic mouse model that produces fully human antibodies, thereby accelerating the antibody development process and reducing associated costs. The Neomab platform is designed to support clients in developing therapeutics more efficiently and cost-effectively. It offers a comprehensive solution by providing a fully human antibody library right from the immunization of NeoMab mice.
Zhang also discussed the immune response capabilities of Neomab mice. These mice have shown a robust immune response against a wide range of antigens, including cytokines, peptides, soluble proteins, and GPCRs. In some cases, NeoMab mice outperformed traditional models, demonstrating their superior immunological capabilities. This robust immune response is critical for obtaining high-quality antibodies for therapeutic use.
Finally, the Zhang briefly touched on strategies to break immune tolerance, which is a mechanism that prevents the body from producing antibodies against self-antigens. The speaker mentioned approaches such as gene knockout and hyperimmune treatment to overcome this challenge. These strategies aim to enhance antibody discovery by broadening the diversity of antibodies that can be produced, even against highly conserved targets.
