Oxford leads European drive on new cancer therapies

21 October 2005

Oxford University is leading a European-wide network to explore the potential of dendritic cell therapy to cure cancer.

Dendritic cells are specialised cells of the immune system that trigger and control many types of immune response. There is considerable interest in using them to treat cancer, HIV and many other diseases, and human trials in advanced cancer patients have already yielded promising results.

The DC-THERA European network is a Network of Excellence established under the European Commission (EC) Sixth Framework Programme. Over the next five years, Professor Jon Austyn from the Nuffield Department of Surgery at Oxford will be leading this ambitious €7.6 million initiative to integrate the activities of 32 European research groups, along with 16 other partners, to translate laboratory findings into clinical trials.

Dendritic cell work is one of the most rapidly-developing areas in immunology today. Several hundred patients with advanced cancer are now involved in a hundred or so clinical trials currently underway around the world. So far there have been encouraging results, with patients’ immune responses increasing, longer life-spans than had been diagnosed for terminal patients on the treatments, and even some regressions of tumours. So far, virtually no side effects have been observed, a huge advantage over current standard cancer treatments.

Scientists create the immunotherapy by taking a cancer patient’s blood, extracting the monocytes (a type of white blood cells which play a role in immune response), and growing them into dendritic cells in culture. Once hundreds of millions of immature dendritic cells have been created they are incubated with antigens from the patient’s tumour. The cells are then stimulated to become mature dendritic cells which, crucially, have now encountered the antigens of the tumour. They are then injected into the patient, where they can potentially initiate the attack against the tumour.

Dendritic cells are ‘sentinels’ that play a role in both the body’s innate immune response (ready and waiting to attack things foreign to the body) and its adaptive response, which, once it is activated by dendritic cells, not only gets rid of invaders but retains a ‘memory’ of them, for ready elimination if they are detected again. This means that if dendritic cell therapy can be used successfully to tackle a tumour, or another disease, the natural response in that patient should be ready to attack if the disease struck again – a major advantage given the rates of recurrence in cancer. In principle, the immunotherapy might even be used in healthy individuals as a vaccine for those who are genetically more likely to develop, say, breast cancer.

Remarkably, certain manipulations may also give dendritic cells the capacity to turn the immune response off as well as on. They could then be used to treat allergies, autoimmune disorders such as diabetes or multiple sclerosis, and transplant rejection, dramatically increasing the scope of the therapy.

‘It’s too early to say whether this could prove a treatment not just for cancer but also for a whole host of other widespread diseases, but the obvious potential is very, very exciting,’ said Professor Austyn. ‘What we need to do now is coordinate what’s going on in Europe, where many of our leaders in the field are situated. We need to standardise the approaches of clinical trials in order that researchers can meaningfully compare what happened in one trial with another and consider all the data as a whole. And we need to make all the different research findings begin to fit together like a jigsaw, instead of overlapping in some places and leaving gaps in others. That’s one main purpose of the network.’

The network will also establish centralised technological platforms, provide training programmes for researchers and technicians, and recruit and educate new PhD students in the field of dendritic cell immunotherapy. ‘Part of the network’s role is the education and training of the next generation of potential European leaders in the field,’ said Professor Austyn. ‘The network will, we hope, spread well beyond the initial partners and survive and develop long after this contract finishes. If we get this right, the potential is enormous.’