Humanized Mouse Models for Preclinical Therapeutic Antibody Development

Adriano Flora, Ph.D. - The Jackson Laboratory

Talk Title: Humanized Mouse Models for Preclinical Therapeutic Antibody Development

Transcript: 

This scientific session is part of a larger cycle of events that focus on a specific topic, namely The Preclinical In Vivo tools for the development of large molecule and antibodies. And the reason why Jax is organizing these sessions is because, we have recognized that it is a certain need for the scientific community to really develop and discuss these tools in the context of drug development.

Large molecules and specifically antibodies are the fastest growing group of new drugs in development, and the reason why is that is mostly because of their high specificity, which is likely to have to lead to less side effects when they're administered to a patient. But these high specificities paradoxically leads to another problem during their development, which is, In Vivo Models are sometimes challenging to use because, antibodies recognize human proteins very well but very often they don't recognize mouse or rat proteins and sometimes not even monkey proteins. So, there really is a need for developing new humanized In Vivo Models to study these molecules during the preclinical development.

Moreover, sometimes the metabolism of these molecules is actively regulated by cellular processes, which might be specific as well. Like the FcRN that we will be discussing today works the human FcRN interacts the human antibodies, interact with mouse FcRn in a different ways that with the human and for this reason, the Jackson lab really has been working very hard to develop mice that express human or human-like features in different parts of their biology. Starting with Transgenic FcRn Mice to test PK of antibodies or Albumin Conjugated Molecules to sell Humanized mice like PBMC Humanized Mice, or CD34 Humanized Immune System Cell Mice to test the immune toxicity or the efficacy at different stages of the pipeline.

Now, today we will be focusing on a specific mouse model Tg32. You will hear a lot about these model in the next hour or so, which expresses the human FcRN, but not the mouse FcRn and can be used to predict how an antibody, the clearance of an antibody in patients. The Fin will present validation data on the use of these model for bi-specific antibodies. And Greg will directly, since we'll focus mostly on the development of different or similar models to cover different applications.