Ex vivo screening of cancer vaccines and virotherapy

Standard anticancer therapies work in many patients but others remain without effective treatments. Drug classes which show huge potential, but which have not yet entered routine practice, include virotherapy (using viruses as therapeutic agents to kill cancer cells) and cancer vaccines (using the patient’s own tumour cells or proteins found on specific cancer types to stimulate the body’s immune system). In Sheffield we are assessing ex vivo drug screening in the EVIDENT trial (NCT05231655). We have established a 2D image-based drug screening models using patient derived cultures which enables us to screen multiple small molecules in parallel directly on patient tissue. We are also developing patient-derived 3D models in parallel. This project will develop methodology to investigate the combination of cancer vaccines and virotherapy. We already have a suite of oncolytic viruses including adenoviruses and Herpes Simplex virus-1 that will be used in this project. These viruses are the most widely studied and have been approved for clinical applications. We are also working with colleagues to develop mRNA vaccines for cancer, and these will also be investigated using our ex vivo models. Importantly, we have developed methods for packaging our cancer vaccines in nanoparticles to improve their delivery to tumours and we will use these methods on patient samples collected in the EVIDENT trial to validate the process. We have funding to carry out RNA sequencing and make bespoke cancer vaccines. The candidate should have a keen interest in oncology, complex cancer models, and therapeutic interventions which can be translated to the clinic. You will be part of the Sheffield Ex-vivo Group working on the EVIDENT programme with Dr G Wells and Prof S Danson, and also the Nanobug Oncology Sheffield team led by Prof M Muthana which focuses on developing state of the art methods to target anticancer therapies to tumours. Collaborations with others in the University with vaccine expertise, such as the Kis Group which is manufacturing RNA- based vaccines and therapeutics, will be encouraged and enabled.

Entry Requirements:

Candidates must have a first or upper second class honours degree or significant research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select (Oncology and Metabolism) as the department.

Enquiries:

Interested candidates should in the first instance contact:

Prof Sarah Danson, [email protected]

Prof Munitta Muthana, [email protected]

Dr Greg Wells, [email protected]