A targeted oncolytic adenovirus to treat multiple myeloma

Details

Project Title: A targeted oncolytic adenovirus to treat multiple myeloma

The research group

The successful student would become a member of the Sheffield Myeloma Research Team with an inclusive, supportive, and collaborative environment where equality, diversity, and inclusion (EDI) are strongly embedded. This includes promoting the celebration of different beliefs, collaboration with other institutions through visits, learning techniques and skills, and attending workshops and conferences to present research findings.

Project overview

Previously we have shown a genetically engineered tumour-targeted oncolytic adenovirus (Ad[SLAMF7 E1A]) recognises, infects and exerts oncolytic effects on myeloma cells (cell lines and ex vivo patient cells) and in myeloma mouse models. However, clinical translation has been hampered as when the virus is delivered intravenously in mouse models others have shown this type of virus is taken up by the liver, thus reducing its efficacy. Therefore, we have begun screening several modified adenoviruses, that have reduced liver uptake in vivo, on myeloma cell lines. We then plan to modify one of these viruses further with SLAM7 (a protein highly expressed on myeloma cells) so the virus only exerts oncolytic effects on SLAM7 expressing cells. We hypothesize a modified adenoviruses will have greater efficacy in vivo models of myeloma than Ad[SLAMF7 E1A]. Initially we will modify an adenovirus, so it is controlled by SLAM7, then assess the ability of the modified adenovirus to infect and induce cell death on myeloma cells. The mechanism/s of myeloma cell death by the modified adenovirus will be determine. Virus and drug combination studies will be performed in vitro on myeloma cell lines, and then the most effective virus and drug combination will be assessed in an in vivo model of myeloma.

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: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying. Candidates will be required to complete a declaration form and upload it to their application.

Please clearly state the prospective main supervisor in the respective box and select ‘School of Medicine & Population Health: Oncology & Metabolism’ as the department.

Proposed start date - October 2024