Prof A MacDonald, Dr J Grainger
Applications accepted all year round
About the Project
IMM-101 is a heat-killed preparation of the environmental bacterium Mycobacterium obuense (NCTC13365) that is currently planning Phase 3 clinical trials for the treatment of advanced pancreatic cancer. In a Phase 2 trial, IMM-101 treatment in combination with gemcitabine, a first line therapy for pancreatic cancer, increased median survival in metastatic pancreatic cancer patients to 7 months, compared to 4.4 months in the gemcitabine only group (Dalgleish et al., BJC, 2016). IMM-101 is thought to be a systemic immunomodulator that induces protective CD8+ T cell responses in vivo, which may have application in a variety of clinical settings. However, the specific impact of IMM-101 on inflammatory networks and immune response development is still poorly understood.
Building on current collaboration between Andrew MacDonald’s laboratory at the Manchester Collaborative Centre for Inflammation Research (MCCIR) at the University of Manchester, and Immodulon Therapeutics Ltd., this project will investigate how IMM-101 influences innate and adaptive immune cell activation and function, using a combination of murine and human in vivo, ex vivo and in vitro experimental approaches. This project will use a combination of cutting-edge techniques (including multi-parameter flow cytometry) to define the proportions, numbers and activation status of key immune cell types influenced by IMM-101, with an emphasis on the skin, dendritic cells and CD8+T cells. Key discoveries will then inform interventionist experiments using in vivo murine inflammatory and cancer models to define the functional outcome and core mediators during IMM-101 modulation of immunity.
Identification of the key cell types and mediators involved in the inflammatory and immunological response elicited by IMM-101 will not only elevate fundamental understanding of how to better use this treatment in cancer, but also provide novel insight into the therapeutic potential of environmental bacteria in inflammation more generally, informing development of such therapies for future use in diverse disease settings.
http://www.manchester.ac.uk/research/andrew.macdonald
http://www.mccir.manchester.ac.uk
http://immodulon.com
This is a potential studentship to be funded via the MRC Doctoral Training Programme. Projects under this scheme are competitively funded; i.e. there are more projects advertised than available
Funding Notes
Please make direct contact with the Principal Supervisor to arrange to discuss the project and submit an online application form as soon as possible. There is no set closing date; projects will be removed as soon as they are filled.
Applications are invited from UK/EU nationals. Candidates from outside of the UK must have resided in the UK for 3 years prior to commencing the PhD in order to be eligible to apply. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
References
1. Dalgleish, A. G. et al. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer. Br J Cancer 115, e16 (2016).
2. Stebbing, J. et al. An intra-patient placebo-controlled phase I trial to evaluate the safety and tolerability of intradermal IMM-101 in melanoma. Ann. Oncol. 23, 1314–1319 (2012).
3. Cook, P. C. et al. A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells. Nat Commun 6, 6920 (2015).
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