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(MRC DTP) Exploiting tumour-promoting paracrine signals in solid cancers to turbocharge genetically redirected T cells

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  • Full or part time
    Dr A Hurlstone
    Prof R Edmondson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

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.

https://www.research.manchester.ac.uk/portal/adam.hurlstone.html
https://www.christie.nhs.uk/internal-lists/consultant-list/thistlethwaite-fiona
https://www.research.manchester.ac.uk/portal/en/researchers/richard-edmondson(fae02acd-600a-4c71-8668-da713f622ce3).html
http://www.cellulartherapeutics.co.uk/people.html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.



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