Novel Therapeutics

For this work package, AllCaN Oesophageal will determine if the use of immune checkpoint inhibitors in BO can affect disease progression. The role of the evolving tissue microenvironment and supportive stromal cells in driving immune checkpoint dysfunction as the disease progresses will also be examined. This will lead to the identification of new immunotherapeutic targets in premalignancy, a largely untapped area for immunotherapeutic development. Cancer immunotherapy, in the form of immune checkpoint inhibition, has changed the face of cancer treatment, including GI cancers. While it uniquely offers the promise of a cure for a small cohort of patients, many patients only gain short-term or no benefit.

The work package will also utilise electroporation; electroporation is the term used when electrical pulses are applied to a cell rendering its membrane porous. As the electroporation pulses vastly increase the porosity of the cell membrane, different drugs, including certain immunotherapies which require internalisation, can be used in combination to facilitate their targeted absorption.

AllCaN Oesophageal will examine the effect of electroporation on the inflammatory microenvironment in Barrett’s non dysplastic and dysplastic ex vivo human tissues and the effect of this secretome on immune cell activation (in dendritic cells and T cells). AllCaN Oesophageal will also acquire additional biopsies (pre and post electroporation) and specifically assess DC’s and T cell biology also in this ex vivo digested material.