From cancer research to innovative applications: The Dutch revolution

Life sciences and biotechnology are widely regarded as one of the most promising frontier technologies for the coming decades with the Netherlands quick to be a part of this revolution. International annual benchmark studies rank the Dutch life sciences industry among Europe's elite, accounting for 10 percent of European life sciences start-ups and ranking 4th in terms of the number of life sciences companies.

“Life sciences is a priority sector for the Netherlands, and we have one that is vibrant and tightlyknit; focusing primarily on research, innovation and sustainability,” says Linnie Mackenzie, Area Director of the Netherlands Foreign Investment Agency (NFIA), a division of the Dutch Ministry of Economic Affairs, Agriculture and Innovation. The sector registers high per capita R&D output and expertise in the areas of healthcare, agriculture and food, environment and general biotechnology.

Cancer research in the Netherlands

The life sciences revolution was born in, and is fed and nurtured by, research. Public research laboratories and institutions of higher education are at the core of the science base, interacting also with enterprise-based research and that of other private bodies.

One of the Netherlands’ main strengths is its science base; centres of scientific excellence in specific technologies exist and are at the core of regional clusters of biotechnology development.

Currently, there are 55,000 life science employees in the Netherlands with about 20 percent of the workforce comprising research staff because of its knowledge intensive nature. Approximately 935 companies are active in the heath-related life sciences industry whilst another 150 companies follow a R&D-focused business model. The country's dense network of world-class universities and research institutes, private sector companies and clinical research organizations, has contributed a great deal to Dutch success in the treatment of some cancers.

In June 2010, the Erasmus Medical Centre (MC) in the Netherlands introduced a treatment method which they hope can beat a deadly cancer linked to asbestos. Researchers in the Netherlands tested the vaccine, which infuses a patient's own dendritic cells with antigen from the patient's tumor on 10 patients and found that it induced an immune T-cell response against mesothelioma tumors.

This is the first time DC-based immunotherapy has been tested in patients with mesothelioma, which typically occurs in the lungs but can arise at other body sites. Asbestos has been banned in developed countries for decades, but the incidence of mesothelioma is expected to continue to increase until 2020. The median survival after mesothelioma diagnosis is about 12 months. The standard chemotherapy treatment improves survival by about three months.

Dendritic cells are a form of immune system cell. The major problem in mesothelioma is that the immunosuppressive environment caused by the tumor will negatively influence our therapy so we are now working on a method to lower this immunosuppressive environment. “We hope that with further development of such a method at the Centre, it will be possible to increase survival in patients with mesothelioma and eventually vaccinate persons who have been in contact with asbestos to prevent them from getting asbestos related diseases,” shares Mackenzie.

The Netherlands’ strong reputation in R&D complements its innovative life sciences sector. Erasmus MC showcases the Dutch’s solid foundation in research. The institute is the largest of the eight university medical centres in the Netherlands and is an internationally recognized centre for high-quality, compassionate patient care, knowledge transfer and development. With a focus in synergizing biomedical, clinical and health sciences research, Erasmus MC is well on the way to becoming one of the world’s leading medical research institutes.

Novel ideas save lives

Life sciences companies in the Netherlands strive to develop and produce innovative medicines and medical devices that enable people to live longer and happier. From world-class companies developing modern technologies in the fields of genomics and medical technology to start-ups developing solutions for applications such as vaccines, therapeutics and diagnostics; their goals all similar – a drive towards exciting innovations for better and more sustainable healthcare solutions.

One of the novel treatments is therapeutic vaccination. ISA Pharmaceuticals develops novel therapeutic vaccines for cancer and infectious diseases by leveraging its proprietary SLP technology to achieve therapeutic efficacy.

An ideal therapeutic cancer vaccine induces strong anti-tumor responses while sparing healthy tissues. This strongly depends on the induction of immunological responses against dominant and subdominant epitopes as well as the induction of co-stimulatory signals. The SLP concept is based on the use of Synthetic Long Peptides for vaccination and when compared to other vaccine technologies, it has a higher likelihood to have a therapeutic effect because it is achieved through the induction of effective CD8+ T-cell and CD4+ T cell responses and co-stimulatory signals as well as induction of strong responses against subdominant epitopes independent of HLA type. Furthermore, SLP vaccination is expected to have a very beneficial safety profile due to its mode of action.

ISA's lead product is a therapeutic HPV vaccine against Vulvar Intraepithelial Neoplasia (VIN) with Cervical Intraepithelial Neoplasia (CIN), and cervical carcinoma as first follow up indications. The company's pipeline further contains vaccines in development against ovarian cancer, colorectal cancer, melanoma and tuberculosis as well as immunomodulating agents such as Adjuvant IS, Toll-like Receptor Based Adjuvants and CD40 agonist.

Impressive clinical results with the HPV vaccine have encouraged ISA to apply its proprietary SLP technology in a broad range of other indications in cancer and infectious diseases. In parallel the company is active in various adjuvants programs to even further improve the efficacy of its SLP vaccines.

For early-stage clinical trials, ISA collaborates with leading medical centers in Europe and the US. Through its partnership with Leiden University Medical Center’s (LUMC) GMP-facility for small batch clinical grade peptide production, the company is in a position to perform crucial clinical trials in a flexible and costeffectively manner.

There lies a strong belief that public-private partnerships are the best way to ensure that fundamental R&D is quickly translated into socially relevant and commercial successful products and services. As such the Dutch government is an active supporter of public-private tie ups such as that offered by ISA and LUMC. European insight

The best way to transfer knowledge is to work together to translate it into practical applications. “The Dutch never shy away from any opportunity to collaborate. Cooperation is in our DNA and we believe that partnerships reinforce the organisational strength of the sector, resulting in an optimal sharing of resources and knowledge,” shares Mackenzie.

It comes as no surprise that the Netherlands is actively a part of one of Europe’s largest efforts in the global fight against cancer. In 2007, efforts were boosted by the launch of the Center for Translational Molecular Medicine, a joint partnership between governmental and private interests, which aims to cut Dutch cancer deaths by 20 percent within the next decade.

It was announced in January 2011 that leading oncology organisations across the region including the Netherlands Cancer Institute, Erasmus Medical Centre and European Cancer Patient Coalition have joined forces in an EU-led initiative titled EurocanPlatform. The project is a network of Europe's 28 most research-intensive institutions in the field of cancer research. The European Union has pledged a generous funding of €12 million. In addition, resources will be put towards finding more effective ways to ensure the prevention, early discovery and treatment of different forms of cancer. EurocanPlatform aims to streamline cross border research. Researchers from the Netherlands, Sweden, Denmark, Norway, France, Spain, Italy, Germany, Hungary, Belgium, and Britain are involved in various parts of the project.

The vast nature of cancer research and therapies available will require greater efforts in research. No one research centre can have the resources needed. The collaborative platform allows individual research groups and organisations to conduct studies they would not otherwise have the resources for; with the costs of expensive equipment, tumour material and expertise shared between them.

“Thanks to continued support from the Dutch government, industry-players and academia, the Netherlands remains at the forefront of life science innovations,” says Mackenzie. A wealth of public–private partnerships acts as an encouraging platform for collaborators from anywhere in the world, she adds.

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Learning from the Dutch

Pharma Asia had a more detailed discussion with Linnie Mackenzie, Area Director, the Netherlands Foreign Investment Agency, to better understand areas where Asia can learn and benefi t from Dutch expertise.

PA: What can Asia learn from Dutch experiences?

Mackenzie: I would say the strong Dutch model of creating strong partnerships between industry and academia, focused clusters, and strong chains linking research to product and business creation is what allows us to compete in the global market. Strong competition afterall leads to high quality products and services that meet the demands of today’s and future markets.

These include products that enable us to detect and treat chronic diseases such as cancer and diabetes at much earlier stages. Also products from the food industry – from plant breeding up to food processing, and the chemical industry where is a growing demand for more sustainable and healthier products and production processes.

The Dutch are also known for their strong organization skills and this is apparent in the remarkably low prevalence of methicillin-resistant staphylococcus aureus (MSRA) in Dutch hospitals, achieved according to experts in large part through meticulous screening and cooperation among hospitals. The same medical infrastructure, encompassing 31 clinical research organizations, 8 university medical centers and 88 regional hospitals working together, has made the Netherlands a favorite place to carry out clinical trials for companies such as Genzyme, Boston Scientific, Merck, Sharp & Dohme (MSD) and Centocor.

We welcome partnerships and platforms from other countries, whether they come from academic backgrounds or from private industry as all stand to benefit from the infrastructure we have built and also the expertise available in the Netherlands.

PA: In your opinion, what are the trends and developments of the Asian pharmaceutical industry?

Mackenzie: The Asian pharmaceutical market will continue to grow. China, India and South Korea are rapidly expanding in this sector. We are also witnessing growth in Vietnam, Philippines and Thailand as a result of the recovering economies, increasing urbanization and the fact that they have to deal with aging populations.

More pharmaceutical giants are moving their R&D operations to Asia – attracted by government support in terms of infrastructure support and incentives.

Countries in this region, including Singapore are aware that successful R&D is the engine that drives economic growth. We are likely to see increased collaboration among privatepublic- government partnerships – in terms of consolidating resources, expertise and funds to develop cutting edge research – with the means to develop commercially viable products.

Rising incidences of chronic and lifestyle illnesses such as diabetes, obesity and heart diseases in affluent Asia populations is creating greater demand for healthcare products and overthe- counter products to treat these illnesses.

Beauty is the new buzz word among Asian women – so slimming drugs, dermo-cosmetic and lifestyle products (promising youth) will continue to push forward.

More importantly, we are likely to see a shift in the pharmaceutical industry, with greater emphasis on the quality of drugs rather than quantity, with health and safety as top priorities.