Harnessing the body’s own immune system should lead to less toxic cancer treatments, says a pioneer in the field of immuno-oncology
Dr Helen Sabzevari is Senior Vice President of Immuno-Oncology at pharmaceutical company EMD-Serono. Sabzevari majored in immunology and immunobiology before going on to do a PhD in immunology, during which she became fascinated by the idea of activating the immune system against cancer. As a result, she went on to do her first postdoc in the fledgling field of cancer immunotherapy. Here she talks to Naturejobs about this growing field of research, and how immunotherapy is changing the treatments on offer for cancer patients.
What is cancer immunotherapy?
In one sense it is looking at how our immune system succumbs to the cancer in the first place, and that makes sense from the perspective that with cancer, the immune system is dealing with its own cells so it’s logical that it would not attack itself. But on the other hand it is fascinating to see how we might train the immune system to recognise cancer cells. For me this is really the dogma I want to address – that on one hand we need the immune system to recognise the serlf versus the non-self, but on the other hand, with cancer, we have to come up with ways to get our immune system to become aware of something that is wrong internally.
After your first postdoc, you switched fields for a while. Why?
It was very clear to me was at that point that in the field if immunology there was a disconnect between cancer immunotherapy on the one hand, and basic immunology and auto-immunity research on the other. Usually these two diseases are opposite sides of a coin – what leads to auto-immunity is over activation of the immune cells, whereas with cancer there is a quiescence of the immune system. My feeling was that it was very important to understand both sides, so I did a senior postdoc in the field of autoimmunity. At the time, some of my mentors did not consider that the best move because I had gained publications and focus in the field of immunotherapy. From my perspective it was completely the opposite – I wanted a holistic view of immunology, in order to come up with more innovative approaches for the immunotherapy of cancer.
During your career have you seen a shift in the way people are looking at treating cancer?
Absolutely. In the past two or three decades the treatment of cancer has been really focussed on radiation and chemotherapy. But the biggest issue there is the toxicity of these treatments. The whole concept of using immunotherapy is to understand how to activate the immune system, which is your own self defence mechanism, and come up with much more innovative therapies that can first lead to the stabilisation of the disease, and eventually work towards a curative aim. This has allowed us to think about approaches that are less toxic, and by reducing the toxicity, patients can maintain the treatment for longer periods of time with a much better quality of life.
What kinds of people are suited to a career in immunotherapy?
It’s unique, in that we need individuals with a good understanding of cancer biology and also a very solid understanding and training in immunology – they can connect this, see the bigger picture, and apply it. Traditionally, most oncologists had just some understanding of the immune system, and immunologists had a very strong focus on immunology and were not necessarily well trained in cancer biology. I think this bridge between the two subjects is something we have seen more and more over the past decade, and immuno-oncology is a really up and coming field.
You moved from academia – working for the National Institutes of Health – to working in a pharmaceutical company. How did you find the transition?
I led the immunology group at the NIH that was working on cancer vaccines. The branch I worked in was very unique in the sense that they had the basic research groups as we well as a clinical group directly attached. This meant were really able to change the paradigm for the cancer vaccine based on the mechanisms of actions we were seeing in our research, and translate that into the clinic. We showed that there really was an alternative to chemotherapy and radiation.
After that, my feeling was that by joining a company that had an excellent portfolio and a very strong history in immunotherapy, especially cancer immunotherapy, I could transfer some of these concepts to a drug format an also to really create a bridge between academic centres and pharma.
How are you building that bridge?
For instance right we are developing a programme that brings postdocs who have completed a PhD in academia into pharma for two to three years. The idea is they can begin to understand concepts of how academia and pharma can collaborate in developing new targets and really bridge the basic research with translational medicine. If these individuals wish they can stay in pharma, or if they go back to academic life we hope they will develop a very strong connection ad collaboration with pharma, which benefits the patients at the end. When I was at graduate school there was always this concept of academia versus pharma and I think the time has come to completely break down these barriers. We need to bring both together as one seamless interaction and really rely on each others’ strengths for the benefit of the patients.
What are you working on at the moment?
I head-up the immuno-oncology reseach at EMD-Serono, and part of the portfolio is cancer vaccines. We already have one in the clinic and we are working on second and third generation vaccines.
What are the biggest challenges in developing a cancer vaccine?
Unfortunately, I think the biggest challenge for the cancer vaccine has been the failures so far over the past two decades. There is a stigma as a result of these failures which has led to the thinking that immunotherapy in general cannot work for cancer. But this isn’t unique to immunology or cancer vaccines – if you look at the history of drug development or even scientific achievements in general, usually it starts with tremendous amounts of failures and then those failures become lessons and generate a lot of knowledge. This leads to progression and eventually success – and this is exactly what we are seeing right now.
Cancer vaccines are moving forward, and we are seeing the first fruits, such as the first vaccine success with [Provenge, which targets prostate cancer]. I think this field is just starting and we will see a lot of other successes in the coming years.
What has been your biggest professional achievement?
To be honest, for me the biggest achievement in my career – and I have not done it yet – will be when I fully put in position a molecule or a drug that has changed the life of a patient. This has been my drive all my life and the bottom line is that this is not about me and it’s not about my career, but this is about the patient. For me that is very personal, and the day I do not take that personally will be the day that I leave science. So, as far as achievements are concerned, for those of us who are in this field, everyday we see patients, and we see families that lose people, and I think it just continuously emphasises that this battle is not over, and this achievement has not been accomplished yet.
For more on careers in immunology, read our feature on the scientists who work to stop a pandemic in its tracks.