Discovery and development of Immunotherapeutics for colorectal liver metastase - CRUK FUNDED at Home UK rate fees
Primary Supervisor: Dr Kerry Fisher
Second Supervisor: Alex Gordon-Weeks
Senior Scientist for day-to-day supervision: Dr Kajus Baidzajevas
Project Overview
This funded project offers a CRUK Graduate Scholarship, providing a living stipend and covering fees at the UK Home rate. Please note, international (Overseas fee status) applicants should be aware that they would need to pay the shortfall between Home and International fees if appointed.
This DPhil project is a rare opportunity to design and develop new immunotherapy treatments for colorectal liver metastases (CRLMs). Our group has developed a unique perfusion technique that enables surgically removed CRLM-containing hemi-livers to be maintained in the laboratory. This allows us to study human tumour biology and the utility of new interventions in a clinically relevant context.
The successful candidate will be working alongside surgeons, spatial biologists and immunologists to develop engineered immune cells that are better able to migrate into tumours and overcome the immune suppressive microenvironment. This will involve tracking the migration and function of labeled immune cells through the capillaries network and across stromal cells layers before entering cancer cell compartment. Rate limiting steps will be identified and overcome using antibody constructs, gene delivery vectors or by directly engineering therapeutic immune cells.
This project will break new ground and will suit a hardworking student with a high capacity for innovation and collaboration within a multi-disciplinary team.
Training Opportunities
The successful candidate will receive training in broad range of laboratory techniques including, advanced pre-clinical models, spatial transcriptomics, molecular biology, and immunology. A broad range of transferable skills including statistics, scientific writing and safety training are provided by the University and Department of Oncology.
References
Freedman, J.D., Duffy, M.R., Lei-Rossmann, J., Muntzer, A., Scott, E.M., Hagel, J., Campo, L., Bryant, R.J., Verrill, C., Lambert, A. and Miller, P., 2018. An oncolytic virus expressing a T-cell engager simultaneously targets cancer and immunosuppressive stromal cells. Cancer research, 78(24), pp.6852-6865.
O’Cathail, S.M., Davis, S., Holmes, J., Brown, R., Fisher, K., Seymour, L., Adams, R., Good, J., Sebag-Montefiore, D., Maughan, T. and Hawkins, M.A., 2020. A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR). Radiation Oncology, 15(1), p.151.
https://link.springer.com/article/10.1186/s13014-020-01593-5