Preclinical Models in Immunology, Immuno-oncology and Immunotherapy
The breakthrough of immunotherapies has unleashed new hope and new success for cancer therapy. However, the choice of a preclinical model is one of the main challenges in the field of immuno-oncology, as they are expected to predict a faithful translation into clinic, anticipating efficacy and tolerability of immunotherapies.
In this webinar, genOway will contemplate the features and present examples of applications of two classes of models in the research of immunotherapies to fight cancer.
Immunodeficient models enable the engraftment of human tumor cells lines, increasing the translatability of the findings. Furthermore, the reconstitution of immunodeficient mice with human immune system gives the possibility to investigate the efficacy and mechanism of action of biologics directed to human targets, with the advantage of exploring the human biology with human tumor cells lines in a mouse model. This presentation will detail the status of human Immune system developed in BRGSF mice and how this model compares to existing immunocompromised models. We will analyze the immune response developed in hCD34+ cells reconstituted mouse and discuss their application for assessment of biologics in vivo. The main limitation of these models is the improper crosstalk between immune system and tumor microenvironment, as the models feature mouse stroma.
A fully functional interaction of immune cells, tumor microenvironment and stroma is provided in a different class of humanized preclinical models, which are the knock-in models. These models display a fully functional mouse immune system with selective targets which have been humanized by gene replacement. The humanization strategy is target-dependent and ensures that the biology of the target, its physiological regulation and interacting partners are preserved. During this presentation we will illustrate the humanization of immune checkpoints such as PD1 and CTLA-4, as examples.
Senior Vice President Discovery - Preclinical Models & Services at genOway