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Reprogramming the innate immune system to treat malignancy: targeting ovarian cancer


Project Description

Despite the major advances achieved in recent years by redirecting the adaptive immune system to recognise cancer cells (notably monoclonal antibodies, checkpoint inhibitors and chimaeric antigen receptor T cells), the therapeutic potential of innate immunity remains underexploited. The innate immune system is an evolutionarily ancient system that enables organisms to detect and destroy invading pathogens, predominantly using phagocytosis by macrophages, neutrophils and dendritic cells. Stimulating phagocytosis by these cells offers potential advantages over approaches using adaptive immune approaches. For instance, it has been difficult to make therapeutic T cells to enter many tissues. In contrast, large numbers of macrophages are present in almost all tissues. Indeed, they may comprise the most numerous cell type in the body and their cytoplasmic extensions infiltrate all tissues and contact most, perhaps all, cells.

The overall aim of this project is to reprogram the innate immune system to recognise, phagocytose and kill ovarian cancer cells. Two ways will be used to achieve this. First, we have identified specific glycan motifs that can stimulate phagocytosis of human cells. This project will use genetic engineering to couple these structures to single chain antibodies specific for tumour associated antigens in order to decorate cancer cells with pro-phagocytic motifs. Second, you will express chimaeric receptors that juxtapose the intracytoplasmic and transmembrane portions of pro-phagocytic receptors with single chain variable fragments that recognise tumour-associated antigens in macrophages. You will investigate whether such macrophages phagocytose ovarian cell lines and primary ovarian cancer cells.

APPLICATION PROCEDURE:
Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM.

Further information on Cancer research at Aberdeen can be found here: https://www.abdn.ac.uk/smmsn/research/cancerabdn-1022.php

Funding Notes

This project is part of a competition funded by the School of Medicine, Medical Sciences and Nutrition for a 4 year PhD programme. Full funding is available to UK/EU candidates only. Overseas candidates can apply for this studentship but will have to find additional funding to cover the difference between overseas and home fees (approximately £15,680 per annum).

Candidates should have (or expect to achieve) a minimum of a 2.1 Honours degree in a relevant subject. Applicants with a minimum of a 2.2 Honours degree may be considered provided they have a Merit/Commendation/Distinction at Masters level.

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