Immunotherapy has revolutionized the treatment of many cancers and research continues to make progress to find increasingly effective treatments. Research and new immuno-oncological therapies, for several years now and with extraordinary results, has been involved in Prof. Vincenzo Cerullo.
Italian, born in Naples where he graduated in chemistry and pharmaceutical technologies at the Federico II University, after an experience in Houston in the United States, he chose Finland, where he brilliantly teaches and leads the Immune-Viro-Therapy laboratory (IVTLab) ImmunoViroTherapyLab, an international and interdisciplinary laboratory that promotes cutting-edge research in the field of oncoimmunology and immunotherapy. We interviewed him, to let us tell about his experience, the most important projects and the goals achieved.
Since few years you are present in the top ten drawn up by Expertscape and considered among the most experienced scientists in the field of oncolytic virotherapy. What is it exactly?
Special genetically modified viruses can selectively infect and kill cancer cells. In this field, we were pioneers to demonstrate that these oncolytic viruses have at least a double mechanism of action. In fact, they are not only able to kill cancer cells directly, infecting and killing them, but they are also able to manipulate the immune system in general and make sure it can recognize the tumor and destroy it.
Can you tell us what was the pathway that brought you here? And why did you choose Finland?
I was born in Naples and I graduated in CTF at Federico II University. After graduation, I planned to continue with research so I started my PhD in part at Federico II and part in Houston, Texas, as exchange student. I got hooked on viruses, especially adenovirus, which I wanted to use to treat genetic diseases. After a brief return to Naples to discuss my doctoral thesis, in 2004 I returned to Houston for a postdoctorate. I spent about six years trying to use adenovirus as a resource for the delivery of healing genes to treat genetic diseases, then a classic "gene therapy", where it is tried to reintroduce the defective gene into the human body using viruses. However, I realized that the adenovirus, perhaps, was too immunogenic to do this; it was a perfect platform as a vaccine but not optimal for classical gene therapy. At one point in my career, I met my wife, we were together in Houston. We got married and were looking for a place to go. There were three options: America, Italy, or Finland. For practical reasons, we have chosen Finland, which remains a winning choice, because my wife and I have the opportunity to work well and the children can grow up in a healthier environment than in other places.
You run the laboratory IVTLab with about 20 researchers who come from all over the world and have very different knowledge and experience: from medicine, computer science, biology and engineering.
We have been and still are at the forefront of everything. Half of the team members are Italian, there are Finns, Spanish and from all over the world.
What does it mean to work abroad with a multidisciplinary team?
This is one of the most efficient ways to work. Beyond stereotypes, the creativity that is often lacking in science, but which should be the fuel of science, is the result of multidisciplinarity and multicultural environment, different people who meet and communicate to put pieces together. There is one thing to say, and this is the big difference between having a team in America and one in Europe. When you put different people to work on the same projects you can do that in two ways: by putting them in competition or by making them feel part of a team, of a story. I chose the latter. You have to show your team that you are working for a beautiful and common thing, that we work together and not against each other, that we are together and not in competition, that we are part of the same fantastic story.
What are you working on now?
A lot of things. We are dealing with cancer vaccine therapeutic, but also with the dream of developing prophylactic vaccines, to make sure one day, that many people who have particular predispositions do not get cancer. We have an excellent platform for vaccines against Covid 19 and many other diseases.
Have you also studied the new coronavirus?
Yes. One of the features where we really pioneered was to have highly flexible and fast cancer vaccine platforms. Cancer is a very fast evolving thing, and our platforms are super flexible, plug and play we call them, where you can mix things and make new drugs ad hoc for a particular tumor. This flexibility and speed had never been considered and applied for infectious diseases; when Covid arrived and it was seen that in these outbreak emergencies was required a flexible and fast platform, we adapted ours.
The relevance of immunotherapy for cancer treatment has been well demonstrated now. But what exactly are immunotherapy and onco-immunology?
Immunotherapy is a way to educate the immune system to fight cancer. Our immune system is able to recognize viruses very efficiently while on the contrary, it fails to recognize tumors. Our immune system doesn't see them, so it doesn't fight them. Our solution to this was to take harmless viruses that are very "visible to the immune system" and decorate them with "pieces of tumor", tumor antigens. When the virus enters, the immune system that does not normally recognize the tumor, is able to see the virus and tries to unleash an immune response against it, but because the virus is 'disguised' as a tumor, the response also affects the tumor and eliminates it from the system. This is the trick.
What's the next challenge?
Decide what these tumor pieces are! I simplified it, saying 'we put pieces of the tumor on the virus, suddenly, by magic, the tumor disappears, because there is an immune response. In fact, figuring out what these pieces of the tumor remain the holy grail immunotherapy.
So these are the questions you are working on.
Yes, in this regard, lately, there is a fantastic work that we have just published in which we have developed our own software that, with an innovative trick, manages to identify among the thousands of possible tumor antigens, those who can be the best by exploiting something that in the tumoral field and had never been done, molecular mimicry.
By the way, recently with your team, you have carried out a study with the aim of understanding how much viral molecular mimicry affects the antitumor immune response in murine and human melanoma. How did the research develop and what conclusions did you arrive at?
Developing this software stems from the idea that autoimmune diseases are sometimes triggered by a viral infection. In a very simplified way, when viruses infect us they trigger an immune response that if it gets out of control can become an autoimmune disease. Viruses have the ability to generate these strong immune responses which need to be controlled. So I started thinking: why don't we try to generate ad hoc autoimmune diseases in which the target tissue is the tumor? Autoimmune disease originates from a violent, unconditional response against a tissue. If we manage to control this and make the target tissue become the tumor, we generate an autoimmune response against your own tumor. This was the basic idea of this work.
This is where the creativity in science falls. You have created a course on this: why did you come up with this idea and what was the goal?
The thing that bothers me is that there are many private companies that are considered extremely innovative and creative. As an academic, this thing is unpleasant to me, academic work should be the real engine of innovation, not private companies. We can do research at very high risk because we do not have to return our investments, indeed the taxpayers pay us to take risks and to explore what has remained unexplored. Most academic science does what others have done and in my opinion deeply betray the mandate of our "investors", the taxpayers. This was my dream, that's why the course was born, the creativity courses, to sensitize students to this mission, this mandate to create innovation. During the course, we also try to understand from a scientific point of view what creativity is and what could be tricks to unleash it!
Among the many interesting experiences you have had in your career, there is also participation in Slush: can you tell us how it happened?
Slush is an incredible start-up and innovation event, which takes place in Helsinki in Finland's darkest period, November-December, when it's dark, there's no snow, it's wet and humid, it's the worst period. It is one of the success stories of Finland because it manages to bring more than 20,000 visitors to Helsinki, I don't know how many millions of online viewers and it is pure innovation. In 2015, for the first time, it was extended to our field, health science. I am invited to speak. I can't remember how many patents we have in my laboratory, but certainly 14 or 15 families, more than 150 accredited patents, precisely because of the great desire to innovate. The first year I pitched my idea of decorated viruses. In 2016, after we founded a spin-off company, which became a success story, I was called back to tell it. I became passionate and in 2017 I created myself together with other colleagues and with the help of the University of Helsinki and the Helsinki Institute for Life Science (HiLIFE), an internal event in Slush, that is called Slush Y Science.
How important is the Italian contribution abroad?
Is critical. Italian creativity in a multicultural team is winning.
At the head of his team there is an Italian, let's attach the medal. Don't you ever think about returning to Italy?
I hate the concept of borders, always! I remember in primary school they asked me where I came from and I said 'from this planet'. My next dream is to build a cross-border laboratory where people, ideas, seminars can exchange efficiently and quickly. I am slowly realizing it because in addition to being a full professor in Finland I am also an associate professor in Naples and there I am building a team of people who already work in close contact with IVTLab in Helsinki, where students and ideas can move without too much bureaucracy to prioritize science and experiments. Returning to your question, why not ?! I often go to Naples to teach and follow my Neapolitan students, teaching at Federico II regenerates me because 'it takes me back to the past, where I come from and reminds me of my path, making me want to offer my students the same opportunities that they were offered to me. In addition, in Naples I have my family, my parents, I am very happy to go. But this is another story not but to mix with the ambition to build a laboratory without borders.
Do you think there will be a therapy tomorrow that can lead to the extinction of tumors? The progress of research has brought great strides, mortality has decreased, but will we be able to defeat this absolute evil?
I am optimistic and I say absolutely yes, I do not know if I will see it, but I am sure that at some point it will no longer be a problem. I don't know what the timeline is, but it will happen; this innovation will not be monothematic, with a drug, but will come out of something very multidisciplinary. I can see innovation.
What makes you most proud of your work so far?
The achievement of du ERC grants, an ERC Consolidator in 2015, when I found out I cried! ERC is the most competitive of all European grants, winning it puts you among the TOP scientists in the world as well as giving you significant funds for at your search. In 2018 I also won an ERC-PoC (proof of Concept) to explore the commenricialisation of some aspects of my ERC-CoG. In the future?? Certainly the day we help a patient.
What is your advice, your message for young researchers, for those who are planning an experience abroad and bring the know-how back home?
The advice is simple! I give it to all my students, get passionate about what you are doing! Enjoy the route and not the destination! Science is like sailing, you do it for the fun of it, without necessarily having to arrive in a place at a certain time! In fact, I'm famous for never giving a project to anyone, I want the project to come from them. The advice is: be passionate about what you do, try to find something that is truly your project, not your boss's project. Be wary of those who entrust the projects to you. The supervisor is essential, he must guide you but he must also let him do it. We try to listen even for months, in an informal way, this is how the innovative part comes out when you are not rational. I often ask my students what their dreams are when we have coffee when we talk about this and that, that's where the projects really are born.