For Dr Juliet Gray, an Associate Professor in Paediatric Oncology at the University, there was little hesitation in choosing her career path.
“I was drawn to paediatric oncology as a medical student. Although it can be a very challenging area to work in, it’s also enormously rewarding. We give children incredibly intensive chemotherapy treatments, and often make children sicker before they start to get better. Parents have to put huge amounts of trust in us for this, and we develop very close relationships with them. One of the first children I helped look after at Southampton was three years old when he was diagnosed with cancer, and spent several weeks in intensive care with complications from his treatment. He has just taken his GCSEs – that type of thing really makes my job worthwhile,” says Juliet.
With paediatric oncology, both science and medicine are closely interwoven, and discoveries in the lab can quite quickly develop into new treatments for patients.
“Paediatric cancers can be very aggressive and grow quickly, which paradoxically means that they can respond better to treatment than many adult cancers. In the 1960s, only around 20 per cent of children were cured of cancer, whereas now it is almost 80 per cent. The progress is tangible, which is exciting,” she continues.
Juliet divides her time between clinical work and research, where a key focus is immunotherapy for neuroblastoma, one of the commonest childhood cancers. Immunotherapy is potentially a very powerful way of killing cancers cells and aims to provide a much more specific treatment than more traditional therapies. It capitalises on the fact that the immune system can recognise subtle differences between cancer and the normal cells of the body and uses this to specifically target and kill the cancer.
There are a number of different types of immunotherapy, which use different components of the immune system. Those using antibodies have shown the most promise in neuroblastoma. Around 100 children are diagnosed each year in the UK, most of whom are very young, usually under five years of age. Sadly, in the majority of these children, the cancer has spread by the time it is diagnosed and the prognosis using traditional therapies is poor, with cure rates of only 30-40 per cent.
In 2010, a large clinical trial in the US reported a 20 per cent improvement in survival in children with high-risk neuroblastoma who had received an antibody targeting the GD2 molecule on neuroblastoma in addition to the standard chemotherapy. Since this breakthrough, most children in the UK with high-risk neuroblastoma have received a similar type of antibody therapy as part of two European clinical trials. One of these trials is led in the UK by Juliet and in the second she is acting as co-investigator. Both trials aim to improve the anti-GD2 therapy, and its side effects on children. The studies have already made it easier and safer for children to receive this immunotherapy, and have reduced their time spent in hospital.
In addition to her key role in the trials, Juliet and her colleagues have been analysing blood samples from children in hospitals across the UK and collecting detailed information on how the antibody is working in children. This will guide how the therapy can be improved further. There are also plans for two new immunotherapy studies for children with neuroblastoma, to be led from Southampton, looking at improving the effectiveness of anti-GD2 antibody by combining with other novel treatments.
“This is a very exciting time for scientists working in cancer immunology. For decades cancer immunologists have believed that the immune system offers a highly specific way of destroying and eliminating cancer cells from the body, but it is only really in the last five years that we have begun to see really positive results come out of clinical trials, with increasing numbers of patients now benefiting from immunotherapies,” says Juliet.
Having completed her undergraduate studies in Cambridge and London, Juliet moved to Southampton for her clinical training, and has been here ever since. She sees huge benefits to working in an environment in which she is surrounded by expertise in all aspects of cancer immunotherapy.
“There have been far fewer cancer immunotherapy trials in children than adults, so we try and look at all the approaches that have been explored for adult cancers, and see what is most applicable and practical to apply to children’s cancers. It’s invaluable to be able to drop by someone’s office or lab and discuss first hand the best way to do something, rather than just reading about it in a journal. Face-to-face collaboration and advice from people you know is crucial” she explains.
The new Centre for Cancer Immunology will concentrate that expertise even further and bring even greater benefits. Alongside practical advantages such as efficient use of expensive equipment, Juliet believes that it will raise the already high profile of Southampton, attracting both “expertise and great minds” wanting to get involved with the cutting edge research, and greater research funding.
She cites two examples as proof positive of this effect in action:
“We have just been selected as one of four sites in the UK to take part in a paediatric trial of a new antibody. It is a type of antibody that is showing enormous success in a number of adult cancers, but there is so far little experience in children. Our involvement is based largely on our reputation as a centre for cancer immunotherapy.
“We are also applying, and have been shortlisted, for funding from a specific grant call designed to generate transatlantic collaboration in paediatric cancer trials. When you look at the number of clinical trials going on in the US, we can sometimes feel like a smaller player, but the Centre gives us more credibility to take on such collaborations.”
Juliet splits her time equally between clinical responsibilities and running her research group, although when dealing with sick children it can be hard to ring fence time for research. “I am very lucky that both elements are on one site and I can dovetail the two. Part of that ability to dip in and out of research labs relies on the critical mass of expertise we have here” she explains.
The advantages of combining clinical and research work are twofold.
“For me, the clinical work and the need to find new treatments are the motivation for the research. But also, the teams that work in the clinic and the lab are very separate, and it is helpful to have a foot in both camps, and some understanding of both aspects to be able to bridge the gap. There may be something in the lab that looks really promising, but for it to be useful to treat neuroblastoma it must be practical for us to deliver to small children.”
Separating work and home life can sometimes be tricky, but Juliet goes home each day to her husband and daughters who, she says, “are very good at making me switch off my phone, and give me plenty of other things to think about!” However, there is always more than enough motivation to go back to work the next day.
“Seeing how children cope with life-threatening illnesses can be very humbling. Really difficult circumstances can often bring out the very best of human nature – in the children themselves as well as their families and the team looking after them. It is one of the most rewarding aspects of my job and a privilege to witness,” she concludes.