Implementation of the patient-derived explant (PDE) platform for evaluating tumour responses to novel immunotherapies

Hypothesis: That the PDE platform enables stratification of patient responses to novel immunotherapies. Experimental Methods and Research Plan: The Leicester Cancer Research Centre is currently the only Centre in the UK with established PDE technology, but a major goal is to expand the platform to other locations. The plan will involve the following: We are collaborating with the Birmingham ECMC through their lead oncologist Prof Gary Middleton, and aim to transfer knowledge and skills to establish PDE technology at Birmingham. PDEs processed at Birmingham from a range of tumor types will be tested with novel immunotherapies developed by Birmingham as well as by our partner organization, LifeArc.mIF and analysis of treated PDEs will be performed at Leicester using digital pathology methods for evaluating tumour and stroma responses to ICIs. We will particularly focus on monitoring the movement of T cell subsets and other immune cells such as macrophages and neutrophils in response to the ICIs. ICIresponses in PDEs will be correlated and integrated with clinical data including molecular profiles, recurrence, progression-free survival (PFS) and overall survival (OS) data. Integration of drug, biomarker, molecular and clinical parameters will be performed using biostatistics and bioinformatics methods. Expected outcomes and Impact: These will be numerous: First-rate training of a young scientist in state-of-the-art technologies ranging from tumour biology, drug discovery and digital pathology to informatics. These will provide the student with unparalleled skills for forging a future career in translational research. Exposure of the young scientist to cutting-edge research environments of Leicester and Birmingham, two of the foremost translational Cancer Centres in the UK. Contribution of key information with regard to continuation/discontinuation of a novel ICI, thus reducing the high attrition rate currently observed in anti-cancer drug development. Development of novel biomarkers predictive of ICI response, which could be incorporated into future clinical studies.