This award aims to expand the chick embryo chorioallantoic membrane model (CAM) to studies of malignant pleural mesothelioma (MPM) to replace the use of mouse xenograft models.
New therapies for MPM are first identified using in vitro immortalised MPM cells. Candidate drugs then undergo preclinical testing in mouse xenograft models. These xenografts use either MPM cell lines or tissue derived from a patient’s tumour. The severity of these studies is classified as moderate under the Animals (Scientific Procedures) Act 1986 due to the level of suffering caused. CAM has previously been validated for breast and pancreatic cancers by Dr Anne Herrmann (Co-Investigator) as part of her NC3Rs David Sainsbury Fellowship. Cells are implanted into the CAM, a highly vascular extraembryonic membrane, where they form a small tumour that can be extracted and used in a number of functional studies to study tumorigenesis, angiogenesis and metastasis. Chick embryos are immunodeficient and could avoid some of the issues of xenograft rejection seen in mouse models, which are reported to have a 40% engraftment rate, creating a bias of MPM cancers that are studied.
Professor Judy Coulson is collaborating with Anne to optimise the CAM for use in MPM research. They will establish robust protocols for engrafting and culturing MPM cell lines and generate standard operating procedures to enable uptake by other researchers. Judy and colleagues will also use CAM in functional studies to screen the effectiveness of therapeutics against MPM and investigate the role of BAP1 – a tumour suppressor with loss-of-function mutations in more than half of all mesotheliomas.