3rd Immunotherapy of Cancer Conference (ITOC3)
Immunotherapy and personalised medicine in review
Prof Paul Sondel - University of Wisconsin, Madison, USA
The most recent focus of our research is really trying to use the immune system to be able to recognise and destroy cancer and it’s no surprise, then, that I’m at this meeting which is focussed on cancer immunotherapy. It’s a wonderful meeting with people who are working at the very basic laboratory level all the way through to large national trials that are designed to test and better utilise the immune system to recognise and destroy cancer and ultimately to have an impact on survival for patients with cancer. Clearly it’s already doing that in many diseases and we’re seeing outstanding progress but I think the progress we’re seeing is only a herald of how this is going to be influencing the way health professionals think about cancer treatment over the next decade.
What directions do you think we will see developments going in, such as in personalised medicine?
Lots of directions, very interesting. Fifteen years ago we had many ideas that were being pursued but we didn’t have the tools to move them into effective clinical testing and trials. Now, because of biotechnology, we’ve got accessibility to many more recombinant cytokines, to monoclonal antibodies that are reactive against a variety of different tumour types, to genetically engineered T-cells that can show reactivity to a variety of tumours, to both small molecules and large molecules that we know can influence the way the immune system works. The concept that’s really coming out of all of this worldwide work is that our immune systems have the capability of rejecting kidney transplants or lung transplants or causing severe immune toxicity and autoimmune disease, we should be able to turn those reactions against a patient’s own tumour; we just need the tools to be able to do it. So yes to our personalised medicine. I think the greatest benefit of the personalised medicine approach is that it’s providing us with the rationale for how to be combining a variety of different approaches that can make a difference for an individual patient. As we think about treating the millions of patients with cancer worldwide, as much as the personalised concepts are helpful in our understanding, ultimately to make this practical and applicable around the world we need to come up with approaches that we can keep in vials in hospital pharmacies that any oncologist at any clinic anywhere in the world can write prescriptions for and come up with the right combination that takes advantage of the appropriate pathways to be able to treat any patient’s cancer. So I think we still will need to be using histologic diagnosis and some molecular diagnosis but in all likelihood we’re going to be doing approaches that will be working for many patients with cancer that have some similarity rather than taking each individual patient’s cancer and looking at each individual patient’s genome, both in their normal immune cells and in their cancer cells and doing the number crunching to come up with the exact unique approach that’s going to be best for that patient. I think we’re learning from that idea but we’re going to have to come up with a way that we can take those concepts and put them into cancer treatment around the world.
So there are many common themes that all of these approaches are utilising and if we can come up with a regimen where we have a way of recognising melanoma for all patients with melanoma and we could use that to recognise the melanoma and then turn on more T-cells to infiltrate that melanoma using that common theme and then cause some tumour destruction at a site to make it more immunogenic, possibly with chemotherapy or radiation therapy, and then combine that with some form of checkpoint blockade, so take the brakes off the tumour. I think this kind of concept will allow us to use these approaches in a really broad way and be treating cancer not only at individual university research centres but at oncology clinics around the world so that we can really take these approaches into cancer patients wherever they are. That really has to be our hope, we need to be able to come up with a practical way of getting rid of cancer for virtually all patients and I don’t think it’s a pipe dream, I think we should see it.
What has caught your eye so far at this year’s ITOC?
The emerging concept that I’ve seen is several speakers have used combined approaches that really put in sequence the concepts that I’ve just described – something to change the tumour microenvironment, whether it’s radiation or the appropriate chemotherapy, to get rid of some of the immune suppression, combine that with something that you can put into the tumour that makes the tumour look much more interesting to the immune system to attract immune cells there and get them interested in killing the tumour in a microenvironment that’s more hospitable to those immune cells, whether it’s a tumour-specific antibody or a TLR agonist or CAR T-cells. Any of these will bring more immune cells into the tumour if you’ve prepared the soil, the microenvironment, to let them function and then take the brakes off. I think this concept is going to be applicable to virtually any cancer that we’re not doing well with using conventional surgery, radiation and chemotherapy and it’s already working. It’s working in virtually any mouse model that we try it in and as long as we set up our mouse models so that they do a reasonable job of simulating what we know we can create in patients this is going to have to translate to efficacy. So I’m very optimistic.
What’s the take-home message for clinicians?
I think that the take-home message is that research is moving slower than we’d like it to. For all of us who have friends or family members or patients we’re involved in with cancer today, they can’t wait for the breakthrough or the small incremental steps over the next ten years. We already have great progress in these forms of immunotherapy coming together, it makes sense to participate in clinical trials, it makes sense to try and get the best therapy for every patient that has cancer now and, at the same time, try and extend our knowledge to be able to do better for patients five and ten years from now. We can clearly look at the way we’re treating cancer now and see how much better we’re doing now than we were able to do ten years ago. It’s continuing to increase exponentially. I think we’ve got to keep the faith and keep working on it because we know we’re going to get there.