In order to develop therapeutics which drive the immune system to target tumour cells and eliminate tumour growth, sophisticated in vitro and in vivo models are required. We have developed models which enable us to combine data from human immune cell in vitro assays and murine pharmacodynamic (PD) and syngeneic tumour models to evaluate which pathways a therapeutic is hitting and whether it is effective at inhibiting tumour growth in vivo. We show here the powerful combination of using TCR transgenic adoptive transfer models and syngeneic tumour with flow cytometry and Nanostring profiling of gene expression within the tumour microenvironment (TME) to determine the effect of therapeutic interventions. To determine the effect of checkpoint inhibitors, mice bearing a defined population of ovalbumin (OVA)-specific T cells are challenged either with antigen (PD model), or an OVA expressing tumour. In the PD model, activation, proliferation and differentiation into CTL are assessed offering a rapid screening tool. In OVA-expressing tumour models comprehensive TIL analysis, can determine how changes to T cell activation impact on the wider TME. Nanostring analysis of gene expression using the murine immune-oncology 360 panel enables a deeper analysis of the TME and acts as a powerful tool for the identification of potential PD biomarkers. This molecular profiling information can also direct which in vitro assays should be used to map the immunological mechanisms underlying immune modulation. Taken together, the use of in vitro and in vivo PD/efficacy models better enable assessment of novel cancer immune therapeutics.
Rhiannon Jenkinson– Associate Director, Cell Biology, Charles River Portishead
Anna Willox– Client Services Manager, Charles River Portishead
Robert Nunan– Group Leader, Cell Biology, Charles River Portishead
Clio Andreae– Senior Scientist, Charles River Portishead
Louise Brackenbury– Group Leader (Autoimmunity and Inflammation), Charles River Laboratories
Tommaso Iannitti– Group Leader (Head of Pharmacology), Charles River Laboratories
Neil Williams– Senior Director of Immunology, Charles River Laboratories