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Lucy Denly

DPhil, Jenner Institute

Improving immunotherapy by defining the interaction between the bacterial vaccine BCG and the host epigenomic and immune response

I am undertaking a DPhil investigating the non-specific immunological and epigenetic effects of the Bacille Calmette-Guérin (BCG) vaccine, which is used to immunize against tuberculosis and is also used as immunotherapy in the treatment of non-muscle invasive bladder cancer. I am particularly interested in the epigenetic changes induced by BCG leading to the phenomena of ‘trained immunity’, and how this may relate to the anti-tumour effects of the vaccine. Amongst other techniques, I will be using TAPS (Tet-assisted pyridine borane sequencing), a new technique developed in the Ludwig Institute, to investigate patterns of DNA methylation in immune and bladder tissue.

How could this research ultimately benefit patients?

BCG treatment reduces recurrent rate and prevents progression of bladder cancer in around 60% of treated patients. However, the non-responsive patients have poor prognosis and high morbidity. Hence there is an unmet clinical need to stratify patients for BCG treatment as well as to understand why the remaining 40% of bladder cancer patients fail to benefit from BCG treatment. Defining the molecular mechanism(s) and durability of these non-specific effects would allow us to stratify patients with bladder cancer who are most likely to respond to BCG, develop more specific interventions and minimise the side effects of BCG. Understanding these mechanisms would also better inform us as to whether BCG based therapy can be adopted to treat cancer types other than NMIBC. 

About Lucy

Prior to my DPhil, I had just completed my 4th year as a medical student at Oxford Medical School. As an undergraduate student I was particularly interested in immunology, however I had not done much laboratory-based immunology before starting my DPhil.