LIMR Immunotherapy: Killing Cancer using Dead Virus

Summary

It is now accepted that our immune systems can hold the key to treating otherwise incurable cancers. So-called “immunotherapy” is an increasingly common method of treating tumours, leading to impressive increases in patient responses.
Immunotherapy usually involves the use of antibodies to antagonise negative regulation of the immune response, known as checkpoints. However, another form of immunotherapy involves using viruses, with the first such therapy now increasingly used to treat melanoma skin cancers. These “oncolytic viruses” (OV) were originally thought to merely replicate within, and subsequently kill cancer cells. However, we now understand that they actually exert a complex and potent effect upon the immune system, generating anti-cancer immunity.

We have discovered that modifying a particular OV such that it is no longer infectious actually improves the ability of this agent to treat liver cancers. Moreover, the inactivated, or “dead” virus also co-operates with current treatment to achieve synergistic therapy. Understanding the response to this agent should not only allow us to improve therapy, but also provide insight into the fundamental biology of protective immune responses targeting tumours within the hepatic microenvironment.

Techniques associated with project
Isolation and cultivation of primary human liver tissue and immune cells, cell culture including up to BSL2 and 3 biological containment, preclinical model experimentation and tissue processing/analysis, immunological phenotyping and functional assays using flow cytometry and other methods, immunohistochemistry and immunofluorescence, western blotting and other proteomic analysis, RNA Seq and associated bio-informatics.

References
Samson; Scott; et al., Griffin; Stead; Short; Melcher. Intravenous delivery of oncolytic reovirus to brain tumour patients immunologically primes for subsequent checkpoint blockade. Sci. Transl. Med. 2018, 10, eaam7577.
Samson; Bentham; et al., Selby; Errington-Mais; Melcher and Griffin. Oncolytic Reovirus as a Combined Antiviral and Anti-Tumour Agent for the Treatment of Liver Cancer. Gut, 2016 Nov 15. pii: gutjnl-2016-312009.

This project is part of the International PhD Academy: Medical Research

In line with the bespoke nature of our International PhD Academy a modified PhD project can be proposed dependent on students interests and background.

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum requirements for this programme in IELTS and TOEFL tests are: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.