Cancer Research UK Clinical Fellow
Curing cancer. One epitope at a time...
Jonathan's team is attempting to engineer novel viral vectors, to harness an immunological phenomenon called 'memory inflation'. They aim to create new vaccines to provide durable treatments for solid tumours.
Jonathan graduated BSc (Hons) in biochemical pathology from St Andrews and MB BChir medicine & surgery from Cambridge, before (in his words) misspending his youth in investment banking. He provided corporate advice and investment analyses, covering then fledgling but now highly successful biotechnology, med tech and pharmaceuticals companies, winning a prestigious StarMine award for the accuracy of his recommendations.
He returned to Medicine in 2012, completing an MSc at the Wellcome Trust Brighton & Sussex Centre for Global Health, with specialisations in pandemic influenza, personalised medicine, and a dissertation to improve the emergency treatment of cholera epidemics, partnered with Médicins Sans Frontières (MSF).
Inspired by Cheng Yeoh, during core medical training (CMT) at the busy Queen Alexandra Hospital in Portsmouth, Jonathan took up an Oncology Fellowship at Oxford’s Early Phase Clinical Trials Unit (EPCTU) supporting phase I/II patient studies to investigate new treatments for melanoma, lung, colorectal, ovarian, prostate and bladder cancers.
Why did you choose your project?
The introduction of immunotherapies has dramatically improved our armoury to combat cancer. However, these treatments are only effective for a minority of patients, typically those 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. From Tim, I began 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, vaccines & adjuvants)
Discovering effective ways to influence that balance, in order to destroy tumours, fascinates me.
What’s your current research?
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 (patent pending) to optimise the delivery and expression of tumour epitopes in murine models of cancer.
We continue to investigate this system, to identify driver and inhibitor factors across a range of important tumour types, with the aim to commence clinical trials of a promising new platform of cancer vaccines.
What does being involved in cancer research mean to you?
It's challenging to explain the emotional rollercoaster that comes with 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 diagnosed early. But ultimately, 90% of us who die from cancer, will succumb to the spread of subsequent metastases.
Cancer vaccines are a potential route to suppress the development of those mets. They may one day save many lives. This goal keeps us going when we're working late in the labs. And remembering all of our incredible patients, their relatives, and our dedicated colleagues across the NHS and around the world. I’m indebted to Cancer Research UK for sponsoring this programme.
CRUK supporting the fight against COVID
Jonathan is currently seconded to the Oxford Vaccine Group, as Lead Fellow to the COV-Boost trial, the first investigation in the world to evaluate the safety and effectiveness of a range of third vaccinations for COVID-19. This will provide urgently required evidence to inform decisions on vaccination programmes for autumn/winter 2021. He is also helping to design a longterm safety and immunogenicity study for the Oxford/AstraZeneca vaccine.
Novel minigene vaccine stimulates CD8+ memory inflation to control growth of murine colorectal tumor
Check out our recent abstract published in the Journal of Immunology