I think the reality is when I started doing this in the UK for a year at St Mary’s nobody believed that antibodies was going to make any difference in the treatment of cancer. So, when César Milstein developed monoclonal antibodies I believe that the patent office had trouble believing that there was going to be a clinical application. I think today in 2016 life is very different and the immune checkpoint inhibitors and antibodies against cancers play a huge role in the treatment of cancer. What I do is clinical trials and I do some pre-clinical animal models as well, particularly to understand why patients are resistant to these treatments. Not everybody responds to these treatments and one of our interests is to understand why that is.
How are you investigating this?
We have to look for the best animal model to do that so you’ve got to get a mouse with a human immune system. We have that and we’re going to do drug testing in these mice with a human immune system and with human cancers and of course nothing beats going to the clinical setting. Human beings, as Sydney Brenner always says, are the best experimental model. We do a lot of phase I clinical trials with not just antibodies but T-cell therapy as well. T-cell therapy is the other big arm of immunotherapy and we have a big interest in that.
What advances do you see in the future of T-cell therapy?
I think it’s interesting, you know the nay-sayers will say it’s very hard to make. Of course, in leukaemias and some lymphomas it’s been remarkable; cures when there used to be none. With solid tumours, you are facing a brick wall which is the microenvironment. Not trying to be pessimistic but it’s going to be a harder job to get good outcomes for solid tumours but people shouldn’t stop trying. We are as a group also focussing on developing better T-cell therapies as well.
Could you talk about your work with aspirin and prevention?
Aspirin has been described as the wonder drug from a thousand years old. It’s from the bark of the willow tree and aspirin is so powerful in cardiovascular and cerebrovascular prevention. The data for chemo-prevention is very compelling - lots of cohorts studied, the Nurses’ Health Study from Harvard. The UK has done many studies which suggest that in certain genetic subtypes like Lynch syndrome aspirin really prevents colorectal cancer development.
What we did was we are trying to look at patients who already have colon cancer but who’ve had surgery and definitive adjuvant chemotherapy. And then we give them aspirin for three years. Another group gets the placebo, so it’s a one to one randomisation, 1200 patients. We are actually at 1000 patients already and we should be finishing the trial next year. The idea is to see whether we can improve survival and reduce relapse with aspirin. We are excited about that because it’s all about giving good and cheap drugs to people and that will give more access to people in the world. As you can imagine, most of the poorer people can’t afford expensive chemotherapy and targeted therapy. The majority of people in Asia are still from the emerging countries, developing countries and you can’t always give expensive drugs to cancer patients.
Could you talk about the research done into the Epstein-Barr virus?
It’s a remarkable story; it’s actually the first virus to be associated with cancer. Sadly, they didn’t win a Nobel prize, I mean Tony Epstein and Dennis Burkett didn’t, nor did Alan Rickinson, that of course went to HPV. I think that the reality is EBV still needs to find a universal vaccine for prevention; that’s being worked on in the UK especially and the US. We treat people with EBV cancers particularly nasopharyngeal. That’s very prevalent in this part of the world, Hong Kong, Singapore, Southern China.
The idea is to target these viral proteins with the immune system and we have done a clinical trial using T-cells to do that, we’ve done a clinical trial using vaccines and allogenic transplants. What we are doing now is perhaps the first randomised phase III trial of T-cell therapy against advanced nasopharyngeal cancer. It will be the first T-cell therapy trial of its kind in a randomised setting against any solid tumour. We are excited, it’s a tough job but 100 patients have been randomised and I think we are on our way there.
What research will be coming out of ASCO and other conferences in the next few years?
A bit more immunotherapy, well you know clinical trials take a long time to mature. I think a bit more immunotherapy. I am hoping to see a little bit more interesting combinations; I particularly like the idea of combinations of not-so expensive drugs with expensive drugs. So, for example, aspirin has been shown to improve immunotherapy in a mouse model. What it does is it recalibrates the metabolomics of the microenvironment in the mouse model and also studies done in London and that makes the immune system around the cancer much more favourable towards attacking the cancer. Very powerful stuff.
