Title : Generation and application of humanized mouse tumor models to expedite translational research for Immuno-Oncology
Abstract:
With the revolutionary progress of cancer immunotherapy, more clinically relevant preclinical animal models are needed to support the efficacy assessment, MOA elucidation and translational research for immune-oncology (I/O) drugs. Humanized murine models have been developed to study the interactions between cancer cells and humanized immune system constructed by transferring human immune cells (T, NK), tissues (fetal liver and thymus fragments), hematopoietic stem cells (HSC) to immunodeficient mice or by using genetically modified immunocompetent mice. With rapid growth of IO animal models in the field, there is a lack of systematic investigation and deep understanding of various models. Selecting suitable humanized animal models for different I/O targets is often challenging for researchers. In order to overcome those technical barriers, we have established multiple humanized animal models, including genetically engineered mouse models and immune cells (HSC, PBMC, NK)-based humanized mouse models and exemplified their utility for the efficacy assessment of different I/O drugs which targeted regulatory T (Treg) cells, T cells and NK cells, respectively. The results showed that each mouse model has its characteristics and researchers must choose and generate mouse models based on the mechanisms of action for each test agent. Based on the systematic analysis of different humanized mouse models, we provide some tactical guidance and some detailed technical guidelines for generation of different humanized mouse models to address specific questions in immuno-oncology translational research.
