Insights of John Haanen, European Society for Medical Oncology (ESMO) Lifetime Achievement Award winner.
Professor Haanen and his team developed a promising new treatment for melanoma, a form of skin cancer. In 2022 alone more than 100 000 new cases of melanoma were reported in the EU.
This treatment, known as tumour-infiltrating lymphocyte (TIL) therapy, uses a patient’s own T-cells, a type of white blood cell that plays a crucial role in our immune system’s defence against infection and cancer. The T-cells are extracted from tumours, grown, and multiplied in the laboratory to make them stronger. They are returned to the human body once the patient has undergone a short course of chemotherapy aimed at creating space for new cells, allowing them to better fight the tumour.
In terms of keeping the disease in check and significantly improving long-term patient survival rates, the treatment far exceeded Professor Haanen’s expectations. It has also opened up new avenues for cancer therapy in general.
John B.A.G. Haanen is Professor of Translational Immunotherapy of Cancer at Leiden University Medical Center and Head of the Medical Oncology Division at The Netherlands Cancer Institute in Amsterdam, the Netherlands. In recognition of his revolutionary contribution to cancer treatment, he received the ESMO Lifetime Achievement Award in September 2024, after also winning the Patient Impact Award, the Netherlands Cancer Institute’s annual award for clinical innovation that has led – or is expected to lead – to significant improvements in diagnostics, survival rates and treatment of cancer patients.
What particularly fascinates you about TIL therapy against cancer, and what has surprised you personally?
John Haanen: We set up the trial in 2013. At this time the melanoma treatment landscape was changing rapidly. This complicated our work, although we had foreseen the arrival of anti-PD-1 drugs. Anti-PD-1 medication helps the immune system to fight cancer by blocking the protein that tumours use to evade attack by T-cells, allowing T-cells to better recognise and attack cancer cells.
We encountered substantial resistance from colleagues who thought that TIL therapy was far too toxic or could never work in patients who had made good progress on anti-PD-1 medication. This was a difficult situation. It took us quite some time to convince colleagues in the Netherlands to refer patients for the trial.
Ultimately, I was very positively surprised by the progression-free survival rate for patients undergoing TIL treatment, that is, the length of time that they live during and after the treatment without their condition deteriorating.
I had never expected the results to be so good
To what extent do lifestyle and environmental factors play a role in this context?
John Haanen: In large parts of the world, virus-induced cancers are endemic. Viruses, especially chronic viral infections, can evade the immune system by inducing a protein found on the surface of T-cells that normally prevents the immune system from damaging healthy cells. Treatment with a type of drug known as an immune checkpoint inhibitor can overcome this evasion process.
In addition, factors such as UV radiation and the chemicals from smoking tobacco can induce chronic DNA damage, which can cause cancer. Again, immune checkpoint inhibitors may help strengthen the immune response to these cancers. TIL is just a type of immunotherapy that has been shown to work quite well in melanoma patients, even where immune checkpoint inhibitors are no longer effective.
When comparing melanoma research with research into colon cancer in Europe, in which area has research advanced more, and why?
John Haanen: Melanoma research has been the poster child for immunotherapy and an example for many other types of cancer research. Therefore, despite the fact that many more doctors work on colorectal cancer, melanoma research is far more advanced.
What are the main challenges in translating research from the laboratory to clinical practice? Is there anything that would make your job at the European level easier from an administrative and organisational point of view?
John Haanen: Clinical cancer research in particular is expensive, and obtaining funding is difficult.
What we have learned is that it may be helpful to convince providers of funding that it is important to support clinical trials that will save money. The reason why we were able to run a randomised controlled phase 3 trial with TIL was because the government in our country had a programme for such trials. We were lucky. Without this support, we would have never been able to run this trial.
Such programmes should not be dependent on luck. In Europe, we should have a programme dedicated to addressing these important clinical questions. In my view, it is time for change, given the high cost of oncologic agents. Otherwise, healthcare costs will soon be unsustainable.
How can we improve academic curricula and professional development programmes at universities to inspire and prepare future researchers for innovative approaches and train them to contribute to the development of advanced therapies?
John Haanen: Curricula need to be adjusted, as immunology in general and immunotherapy in particular have a central role to play in the fight against many types of disease: cancer, autoimmune disease, cardiovascular disease, infectious disease and neurodegenerative disease.
It is essential that young doctors and scientists better understand the biology involved. A key problem, in my view, is that we need more clinician-scientists. The required stress-resilient young people who are willing to go the extra mile to excel in their job appear to be a rare breed. Finding such people is not easy, and it requires good mentors and stimulating research environments too.
How can we enhance collaboration and communication between scientists, oncologists and policymakers to ensure that patients benefit from cancer policies and clinical practice based on the latest scientific research?
John Haanen: This requires the combined effort of many different entities, such as the European Society for Medical Oncology and European funding programmes such as Horizon Europe.
Unfortunately, change is never swift. Science takes time, and convincing at times very conservative regulatory and funding bodies can be a drawn-out process.
