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Exploiting tumour-promoting paracrine signals in solid cancers to turbocharge genetically redirected T cells


   Faculty of Biology, Medicine and Health

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Adoptive cell therapy (ACT) using tumour infiltrating lymphocytes (TILs) or genetically redirected T cells are some of the most promising approaches to emerge recently for the treatment of metastatic disease. However, the tumour microenvironment (TME), comprising extracellular matrix and multiple stromal cell types, is often unconducive for effector T cell activity, limiting the effectiveness of ACT. TME is not typically incorporated in in vitro assays used to assess the efficacy of genetically redirected T cells, leading to poor predictive power. Here, we propose constructing a 3D co-culture system better representing the TME, which should therefore be more predictive. Furthermore, the TME contains soluble paracrine signals that are important for the homing of several leukocyte subsets which foster immunosuppression and that promote the proliferation and survival of transformed and stromal cells in the TME. Of note, the intracellular signalling molecules that relay migration, proliferation and survival signals to the nucleus are broadly overlapping in effector T cells and transformed and stromal cells in the TME; specificity comes from the receptor-cognate ligand pairs. We now propose further engineering genetically redirected T cells so they can respond to signals intended for transformed and stromal cells within the TME in order to couple tumour-promoting paracrine signals to their migration and cancer reactivity of genetically redirected T cells.

Training/techniques to be provided: molecular biology, cell culture, microscopy, in vivo models

Eligibility

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website).

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