This is a meeting of the Association of Cancer Physicians which is about immunotherapy so all of the talks, including mine, are largely celebrating the very real progress that’s been made in immunotherapy, the excellent results that are being seen, among other things, but particularly with checkpoint inhibitors and the way in which the clinical research community is beginning to work out how to use those to produce the maximum benefits for patients, the maximum safety for patients, recognising and treating toxicity when that happens but most of all focussing now on the potential of these new treatments for cancer to produce long-term benefits for patients, long-term survival but not for everybody. So the focus, then, of my talk is on seeing this level of success, how do we progress this, what experiments do we need to do to understand what’s happening and perhaps to come up with the next generation of ways of both using these sorts of treatments but also adding in the appropriate vaccines that will stimulate a better immune response, perhaps, for more patients.
What do we need to do to progress?
We need to understand more of the biology of where the success comes from. That knowledge is growing so we understand the basic biology of, for instance, checkpoint inhibitors but we need to understand what the targets are to which the immune responses that they promote are working. So is that important? The evidence seems to be that it is. What are the parts of the targets of the immune response, what the relevant antigenic determinants will be that we need to target and can we build on that to increase the number of patients who benefit, so perhaps adding a target-based vaccine to the checkpoint inhibitor, that sort of approach.
Can you elaborate on this particular vaccine?
Yes, the particular vaccine that I’ve been talking about comes from a collaboration which I greatly enjoy with a colleague, Richard Vile from the Mayo Clinic. So the idea, Richard’s idea, was to take an oncolytic virus, and he used a vesicular stomatitis virus, and to use that to generate a library of viruses, each containing a small component, cDNA, from the tumour and in that way to have a reagent that covers a wide range of possible antigens on the surface of the tumour but also that they’re being presented in the context of a virus which is a good way of stimulating an immune response. So I was summarising the evidence that that works very well in model systems, one of the most exciting findings recently in model systems in immunotherapy. So a key challenge – can we take that into the clinic? How do we do that? What virus do we use? We’ve been talking about experiments using an adenovirus which is a safe, easy to give virus that can be used in people. Can we make a library? The answer is yes. Does it work in the mouse? Yes it does. Can we translate it into the clinic? Remaining large challenge.
So is somebody going to take up this challenge?
I hope so. We’ve more experiments to do, obviously, to give a good body of data to support that but it’s a challenge indeed because of the complexity of the library but the actual making of the reagent is relatively simple compared to some of the other immunotherapies. Regulators will have very strong views about the safety of this, that has to be tackled, and the doses have to be got right. There’s a lot of work to do but potentially it can go into the clinic, people will take up that challenge.
What is the main message from your talk?
Immunotherapy for cancer is genuinely now showing patient benefits. There are patients who are surviving in the long term who would not otherwise have done so. But the proportion of patients who are benefitting is not good enough so there are some cancer types for which we’re not making progress – pancreatic cancer, prostate cancer particularly. So we need to understand that better and focus on that. Then even where you have cancers that are responding to the treatments well like melanoma and kidney cancer there are still quite a lot of patients with those cancers whose benefits are very limited. So we need to understand that better to grow the number and to design clinical approaches that will benefit more people.
