First published in AMS magazine. Authors: Jayne Robinson and Ed Aanhane

Amsterdam’s entrepreneurial spirit is woven into its very essence; the city continually moves to the forefront of various fields with its new and innovative ways of thinking. And it’s this evolutionary attitude that makes the city a worthy match for an equally agile and ever-adapting field of research: oncology, the study and treatment of cancer. Since the unravelling of the human gene sequence in 2003, huge leaps have been made in the field of human genetics. Cancer research has naturally evolved alongside these advances, and the approach to therapy has shifted from broad, one-size- fits-all treatments to personalised ones tailored to the individual. Although radiation, surgery and chemotherapies are still widely used today, the insight that no two tumours are alike has led to a greater focus on tailored medicines that offer high efficacy, new methods of early detection and, ideally, reduced side effects.

At the heart of this new wave of cancer research are the laboratories of Amsterdam, home to some of the world’s leading experts and a hotbed for game-changing new developments in the field. With a population of just under 800,000 – that’s one tenth the size of London or New York – the city of Amsterdam is relatively small in comparison to its global peers. But its size is a factor that works to the city’s favour in many ways, gifting it an agility and responsiveness that helps things to move quickly. Additionally, Amsterdam is known for its close-knit, collaborative communities that work together to achieve great things. Nowhere is this approach more evident – and more valuable – than within Amsterdam’s biomedical circle: a thriving network of institutions and companies built on sturdy foundations, fuelled by new ideas, and supported by strong initiatives that make for one of the most effective cancer research hubs on the planet.

A research hive

With many established oncological research institutes calling Amsterdam home, the city has been a globally recognised hub of cancer expertise for over a century. The Netherlands Cancer Institute (NKI), the Vrije University Medical Center Cancer Center Amsterdam (VUmc CCA) and the Oncologic Research Centre AMC (ORCA, part of the Academic Medical Center) are all located in Amsterdam, employing a combined workforce of nearly 9,000 people, and producing around 4,000 scientific articles every year.

To preserve and promote knowledge for future generations to build on and to ensure that Amsterdam continues to drive the field of oncology forward, these three institutions have united to create the Oncology Graduate School Amsterdam (Onderzoekschool Oncologie Amsterdam, or OOA). The OOA employs around 500 PhD students and produces over 1,900 scientific papers each year. It plays an active role in Amsterdam’s oncological community, organising regular events and meetups to promote the exchange of knowledge and hone the expertise of its students. But to optimise and share the information generated at these research institutes and to ensure that their findings can impact real lives, it is important that knowledge be translated from the lab bench to the bedside as quickly as possible. Amsterdam has devised some impressive ways to achieve this.

Bringing science and business together

Nothing fosters a sense of community like close physical proximity. So two science parks were created, to promote the integration of oncological research from Amsterdam’s major and minor institutions into the developments of the companies that can best utilise it. The Amsterdam Science Park and the Medical Business Park offer companies high-tech business premises amongst the scientific institutes and faculties, removing geographical obstacles to their effective collaboration. The parks equip businesses with all the latest facilities, as well as a fibre optic network to connect everyone and promote quick data analysis. The Innovation Exchange Amsterdam (IXA) acts as the go-between for Amsterdam-based academic institutions and parties interested in their research findings: for example, companies, educational institutions, investors, healthcare providers and government bodies.

Researchers require assistance from companies when it comes to increasing the social and economic footprint of their scientific work, while companies need help in finding business opportunities or tailor-made solutions for problems. It’s a relationship that benefits all, so the IXA was established with the overall goal of providing societal impact from science. A conglomeration of the various Technology Transfer Offi ces (TTOs) of five Amsterdam institutes, the IXA brings together their accumulated knowledge and drives the transition of scientific discoveries into groundbreaking insights that can benefit society in a number of ways.

One vivid example of the benefits of this integrated approach is the newly established Hartwig Medical Foundation tumour DNA database. This non-profit organisation, which opened its doors in the Amsterdam Science Park in February 2016, uses the latest sequencers to track the individual characteristics of the tumours of all cancer patients in the Netherlands. Combined with the patients’ clinical data, the organisation strives to promote new cancer treatments and to refine current strategies. Having direct access to this kind of facility is undoubtedly invaluable for hospitals, research institutes and companies alike. Another recent success story of this collaborative approach is thromboDx, the molecular diagnostics company established in 2012 to house Dr. Tom Würdinger’s groundbreaking neuro-oncology research at the VUmc CCA (and recently acquired by San Diego-based sequencing company Illumina).

Facilitated by the IXA, Dr. Würdinger and his team – in collaboration with laboratories from Umeå University in Sweden, Harvard Medical School and Massachusetts General Hospital in Boston – developed a blood-based diagnostics platform that is able to identify the location of the primary tumour and guide therapeutic decision making. They discovered that platelets in our blood can be ideal cancer biomarkers, carrying a tumour’s genetic information, thus enabling doctors to detect tumours by means of a blood test, with no need for a biopsy. Würdinger now works for a number of institutions, from the VUmc and Harvard Medical School to Illumina start-up GRAIL, where, as Director of Nucleic Acid Biology, he is working on a global cancer blood test. In addition to the (financial) support of VUmc’s neurosurgery department, led by Professor Peter Vandertop, and the VUmc Liquid Biopsy Center Amsterdam (since 2016, the fi rst Dutch blood bank for cancer research), Dr. Würdinger cites the IXA, and in particular the Technology Transfer Office of the VUmc, as key factors in facilitating the transfer of thromboDx from the lab to a commercial venture. ‘The TTO from the VU was crucial,’ he enthuses. ‘They assisted the inventors in getting the appropriate patents, they helped us to put the initial business case together, and they supported us with funds and access to their network.’

A personal approach

Another recent shift in the development of personalised cancer treatments with its roots firmly planted in Amsterdam laboratories is immunotherapy – i.e., treatments that harness the power of the immune system to fight cancer. Immunology has been in the international headlines recently, with scientists confident that it could form the backbone of new cancer treatments in the coming years. Just as every person’s genetic makeup is completely unique, so is every tumour. While two people can be diagnosed with the same type of cancer, the genetic backgrounds of their tumours are likely to be very different. That’s why eminent researcher Dr. Ton Schumacher and his cancer immunology research groups at NKI (in collaboration with groups from the TUM School of Medicine and Stage Cell Therapeutics, both from Germany) have been working hard in the field of T-Cell receptor therapy to help develop tailor-made treatments that weaponise the body’s own immune system to effectively fight cancer. This type of therapy helps the immune system to destroy harmful cancer cells by cloning the patient’s own T-cells (which already have the ability to eradicate diseased cells), swelling their numbers in a lab, and reintroducing them back into the body to fight the cancer. However, T-cell therapy currently involves a process that can be difficult and time consuming (the custom isolation and characterisation of tumourspecific T-cells from each patient), and doesn’t always yield high-avidity T-cells. And when a patient needs treatment right away, designing a personal vaccine is impractical.

Through his work at NKI, Professor Schumacher has found a way to overcome the hurdles that were preventing T-cell therapy from becoming an efficient and commercially viable treatment. His solution is to generate a high-throughput platform that speeds up the process of isolating tumour-specific T-cell receptors and selecting the ones with the highest efficacy. The T-Cell Factory (TCF) was established in 2014 to house the patents and intellectual property of the platform. Seeing the far-reaching therapeutic and commercial possibilities of the project, biopharmaceutical company Kite Pharma acquired TCF in 2015 for an upfront payment of €21 million and additional milestone achievement-linked bonuses that could well surpass the €250 million mark. As Dr. Tanja de Gruil, who specialises in translational tumour immunology at the VUmc Cancer Center points out, ‘high-profile multimillion-dollar deals like the takeovers of the T-Cell Factory and thromboDx demonstrate how the infrastructure in these Amsterdam research institutes supports the entire gamut of translational research, from lab bench to bedside.

Tomorrow’s talent today

Of course, it should never be forgotten that all of Amsterdam’s big-hitters in cancer research, whether they’re gracing the cover of New Scientist or dealing with commercial offers from the world’s top pharma brands, are continuously giving back to the city’s academic circles via professorships and expert guidance. Undoubtedly, one of the true strengths of Amsterdam isn’t just the research organisations and initiatives already in play, but the talent continuously feeding into the system of graduate research. These days, the University of Amsterdam and the VU are working hand in hand to strengthen scientific education throughout the region under the banner ‘Science in Amsterdam’, a targeted campaign that reaches out to potential students at home and abroad looking to delve into bachelor’s or master’s programmes. And for those students who have a keen sense of what they want to achieve from the outset, the VUmc CCA provides a ‘lifelong learning’ programme that reaches out to scientific talents at secondary schools, guiding them towards (bio)medical bachelor programmes, research masters in oncology and onwards into the doctorates and postdoctoral roles of the previously mentioned Oncology Graduate School Amsterdam.

As someone who is not only heavily involved in Amsterdam’s cancer-research scene but also in teaching the next generation, Dr. Würdinger is not surprisingly proud of the efforts currently in place to attract potential students and prepare them for clinical and academic roles at leading institutions around the world. ‘The Netherlands truly has an outstanding schooling system, as compared to most, if not all, other countries. It means we can train great people,’ he says. ‘And when you also consider that we have the largest university hospital here and the ongoing integration taking place between the AMC and VUmc, the other cancer-focused research institutes and now the Dutch Cancer Society right here in Amsterdam, it’s no surprise that the city is enjoying so much success when it comes to breakthroughs in cancer research.