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


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.

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

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject

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. For more information please visit http://www.internationalphd.manchester.ac.uk

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). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

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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