DPhil, Nuffield Department of Medicine
Project: Development of Novel Cancer Vaccines to Harness Memory Inflation Driven by Adenoviral Vectors
Jonathan investigates the development of Novel Cancer Vaccines to Harness Memory Inflation Driven by Adenoviral Vectors
Jonathan graduated BSc (Hons) in biochemical pathology from St Andrews and MB BChir medicine & surgery at Cambridge, before (in his words) misspending his youth in investment banking, where he provided investment analyses and corporate advice for biotechnology, med tech and pharmaceuticals companies.
He returned to Medicine in 2012, completing an MSc in Global Health at Brighton & Sussex Medical School, with specialisations in pandemic influenza, personalised medicine, and a project to improve the emergency treatment of cholera epidemics with Médicins Sans Frontières (MSF), while retraining.
After core medical training (CMT) at the busy Queen Alexandra Hospital in Portsmouth, he took up an Oncology Research Fellowship at Oxford’s Early Phase Clinical Trials Unit (EPCTU) supporting phase I/II patient studies to investigate new therapies for melanoma, lung, colorectal, ovarian, prostate and bladder cancers
Why did you choose your project?
The introduction of immunotherapies has dramatically improved the armoury of therapies to treat cancer. However, these treatments are only effective for a minority of patients, typically suffering from tumour types carrying the greatest frequency of somatic mutations. I was fortunate to become involved in a DNA damage repair inhibitor programme with the Humphrey Group. At Oxford, I have begun to understand that there is a complex interplay of DNA disruption (ie. how broken is your cancer, so that the immune system can recognise it), tumour self-protection mechanisms (microenvironment and local immune downregulation), versus interventions to enhance immunogenicity (with cytokines, antibodies, adoptive cell therapies or vaccines).
What’s your current research and how could it impact patients?
Paul Klenerman developed the immunological concept of memory inflation, where certain common viruses are capable of stimulating persistent, long lived CD8 T-cell responses, instead of the conventional rise and fall. Harnessing this, our team has developed a Mini-Gene technology to optimise the delivery and expression of tumour epitopes in murine models of cancer. We continue to investigate this system, to identify the driver and inhibitor factors, which we hope will lead to future patient trials of a platform of cancer vaccines.
What does being involved in cancer research mean to you?
It is difficult to explain the emotional rollercoaster of being a cancer physician. Statistically, cancer is a burden that 1-in-2 of us will face. Modern surgical and radiotherapy techniques offer hope, when the disease is caught early. But ultimately, more than half of us who die from cancer, succumb to the spread of later metastases. Cancer vaccines are a potential route to suppress the development of these mets. They may one day save many lives. So when we’re working late in the lab, this thought keeps us going. And remembering all of our amazing patients, their relatives, and our superb colleagues across the NHS and around the world. I’m indebted to CRUK for sponsoring this programme.
Link to our recent abstract in the Journal of Immunology → https://www.jimmunol.org/content/204/1_Supplement/169.36