In this presentation, Sebastian Warth from Charles River discussed the use of humanised mice in the development of immunotherapy, primarily focusing on oncology applications but also addressing autoimmunity and inflammation. Charles River aims to provide integrated drug discovery expertise through its extensive capabilities and collaborative approach with clients.
Charles River has invested significantly in enhancing its offerings, acquiring various companies to expand its integrated drug discovery services. Notably, over the past decade, the company has been involved in over 80% of FDA-approved novel drugs. The company's oncology division operates from multiple sites, including North America and Europe, providing a wide range of in vivo models, such as patient-derived xenografts (PDX) and syngeneic models.
The in vivo models available at Charles River include: PDX Models: These are created by implanting primary patient material into immunodeficient mice, allowing the model to retain the characteristics of the original tumour. CDX Models: Tumour cell lines are engrafted onto immunodeficient mice, enabling efficacy and survival studies. Syngeneic Models: Utilised for studying immune responses in a more natural setting.
Humanised mice are genetically engineered models that incorporate human immune cells, making them crucial for testing therapies targeting human-specific agents, such as checkpoint inhibitors and bispecific antibodies. These models are particularly valuable for assessing immune cell functions and the effectiveness of immunotherapies.
Warth emphasises the significance of humanised T cell models, where tumours are implanted in immunodeficient mice, and T cells are cultured from peripheral blood mononuclear cells (PBMCs). The response of these models to various treatments can vary based on donor variability, highlighting the complexity of immune responses.
Charles River also explores the use of CAR T cells in humanised mice, demonstrating their efficacy in specific cancer models. Additionally, the company has developed CD34 humanised mice, which allow for the differentiation of hematopoietic stem cells into various immune cells, enhancing the study of immune responses to tumours.
Warth discussed the creation of tumoroids from PDX tissues, which can serve as in vitro avatars for studying tumour responses and correlating with in vivo outcomes. This innovation allows for a more efficient evaluation of potential therapies before moving to in vivo testing.
In conclusion, the presentation highlights the vital role of humanised mice in cancer therapy development. Charles River's commitment to advancing these models and their applications in immunotherapy underscores the importance of collaborative efforts in drug discovery. The integration of in vivo and in vitro approaches provides a comprehensive framework for evaluating therapeutic strategies, ultimately contributing to more effective cancer treatments.
