Unleashing the body’s own immune system to cure cancer
When the 2018 Nobel Prize in Physiology or Medicine was presented to James Allison of the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo of Kyoto University in Japan, it was not only a reward for research that has given cancer patients hope in the future. It was also recognition of therapies that are already curing many of them.
In Western Switzerland, the extraordinary potential of immunotherapies has been embraced enthusiastically by researchers, clinicians, academia and companies. Professor Olivier Michielin, chief medical officer of the division of personalised analytical oncology at the Lausanne University Hospital (CHUV) explains: “The clinical results are so spectacular for some pathologies that, for a small number of patients, we no longer measure survival in months but in years. There is even the possibility that some can be cured, though it is too early to say that with any certainty.”
The promises of immunotherapies have triggered all kinds of initiatives that are gathering forces from academia, pharma and biotech in the Lake Geneva region. The Swiss Cancer Centre now brings together more than 80 research groups. At the new Agora Centre at the CHUV, partners such as the ISREC Foundation, the CHUV, the University of Lausanne, the Swiss Institute of Technology of Lausanne (EPFL), the Ludwig Institute for Cancer Research, the University Hospital of Geneva (HUG) and the University of Geneva gather together 300 researchers and clinicians to develop and apply new cancer therapies under one roof.
« The promises of immunotherapies have triggered all kinds of initiatives that are gathering forces from academia, pharma and biotech in the Lake Geneva region. »
Still, immunotherapy is not the long expected magic bullet against cancer. The Nobel Prize-awarded checkpoint immunotherapies only work for a limited number of patients. Activating the immune system may also trigger autoimmune side effects. There is still a great deal of research to be done, if only to make such therapies more accessible, including in terms of pricing.
That is where the cluster effect of the Health Valley of Western Switzerland plays a major role. As readers will discover, the region is home to many institutions and companies which are translating research from the labs to the patient’s bedside in various fields beyond cancer.
Source: cancer Research UK
Source: Ligue Suisse contre le cancer
Immunotherapy, a leverage for a massive scaling-up in life sciences
On October 3rd 2018, a futuristic new building, the Agora, became home to 300 researchers and clinicians in 25 different specialties. Their objective: to discover and accelerate the transition of novel oncology treatments from labs to patients. Located at the heart of the Lausanne University Hospital (CHUV) campus, Agora brings together multi-disciplinary teams of doctors, biologists, immunologists, bioinformaticians and bioengineers from the different partner institutions: the Swiss Institute for Experimental Cancer Research (ISREC), the University of Lausanne (UNIL), The Swiss Federal School of Technology (EPFL), the Lausanne University Hospital (CHUV), the University Hospital of Geneva (HUG), the University of Geneva (UNIGE)and the Ludwig Institute for Cancer Research Lausanne.
The microenvironment of Professor Coukos
Immunotherapies, both at research and clinical levels, have been instrumental in creating this new facility -which is the flagship of a network of academic institutions, pharma and biotech in the domain of immuno-oncology. It is creating the critical mass for the region to become a world class hub in the fight against cancer.
Professor George Coukos, who is both the head of oncology at CHUV and director of the Ludwig Institute for Cancer Research in Lausanne, explains: “For research and therapies that were predominant until 10 years ago, cancer was seen as the result of genetic alterations and the tumour cells themselves as privileged targets. It drove chemotherapies and later targeted therapies. But we came to realise that these approaches were largely not curative but palliative.”
In other words, these therapies were playing a major role in slowing tumour growth, but cancers were finding ways to overcome this suppression. Cancer research then started to make important progress towards understanding how the disease works and what could provide important leverage to gain therapeutic momentum.
Agora, the epicentre of Western Switzerland’s ambition for oncology.
Hacking the immune system
One of the main reasons cancer cells thrive unchecked is that they are able to hide from the immune system. So, certain immunotherapies mark cancer cells to make it easier for the immune system to find and destroy them. Others boost the immune system to work better against the cancer. In all cases, they help the body to heal itself.
Today there are several types of immunotherapies used to treat cancer. Checkpoint inhibitors work by releasing the brakes that keep T-cells – a type of white blood cell – from killing cancer cells. Adoptive cell transfer is a treatment that attempts to boost the T-cells' natural ability to fight cancer. Finally, monoclonal antibodies are immune system proteins created in lab. With targeted therapies they are designed to attach to specific targets found on cancer cells and stop them growing. But some monoclonal antibodies also mark cancer cells so that they will be more easily seen and destroyed by the immune system.
In Western Switzerland all kind of initiatives are now in place to improve immunotherapies. For example, Lausanne-based pharma Debiopharm is developing various approaches to enhancing anti-tumour immune response. With the vast majority of its immuno-oncologic drugs produced or developed at its sites near the Lake of Geneva in Aubonne and Corsier-sur-Vevey, Merck, as part of the Merck-Pfizer Alliance, has co-developed and co-commercialized an anti-PD-L1 monoclonal antibody Avelumab for the treatment of metastatic Merkel cell carcinoma (a rare but aggressive skin cancer) as well as for the treatment of pre-treated patients with locally advanced or metastatic urothelial carcinoma (bladder cancer) in the US, Merck is also engaged in various development programmes often targeted to enhance immune response.
Boosting the immune response is also the core of the technology developed by Geneva-based biotech MaxiVax. Its technology consists of a very small encapsulating device which is placed under the skin. It is composed of irradiated tumour cells from the patient as the target for the immune response and a strong immunity booster (GM-CSF: granulocyte-macrophage colony stimulating factor), released from an encapsulated, genetically modified cell line.
Doug Hanahan, director of ISREC, is following the same kind of combinatory approach in his lab. "We’ve long suspected that tumours can develop multiple and diverse barriers to avoid infiltration and killing by immune cells. By breaking these barriers it may be possible to empower the immune system to kill cancers”. His lab is developing mechanism-guided immunotherapy strategies to disrupt multiple tumour barriers operative in cervical carcinomas in order to effectively unlock tumour immunity.
At University Hospital in Geneva, Professor Pierre-Yves Dietrich, head of the oncology department, has been leading research at the Tumour Immunology Laboratory of the University of Geneva to develop immunotherapies in the brain, an organ which is difficult to access and where any mistake could have huge consequences. After establishing the existence of antiglioma immunity, his team discovered ten novel glioma-associated antigens with high expression on tumour cells. Importantly they do not express on normal tissues, an indispensable feature to avoid autoimmunity. “This advance has allowed us to initiate clinical trials of peptide vaccination in patients with gliomas that is currently under way”, explains Dietrich. But his group is also active in the development of T-cell therapies in collaboration with Professor Carl June’s lab at the University of Pennsylvania.
Beware the immunotype
Despite the hope immunotherapies will treat many cancer real application are still limited.
(Percent of cancer deaths in the US potentially treatable by immunotherapy drugs in 2017)
Source: Talia Bronshtein / STAT Source
CAR-T cells therapies on the rise
One immunotherapy approach, the so-called CAR T-cell therapy (CAR = Chimeric Antigen Receptor), consists of isolating T-cells from patients and to engineer these cells by integrating the gene coding for a special recepetor that binds a specific protein expressed on the patient's cancer cells. When these engineered T-cells are re-injected into the patient they can specifically attack the patient's cancer cells.
At the Institute of Life Technologies at the University of Applied Sciences in Wallis, Professor Gerrit Hagens is developing CAR T-cell-based therapies to treat patients suffering of certain leukemias or certain solid tumours.
« We are developing these therapies together with industrial partners. [...] Once developed the technologies will be the transferred to the Swiss Biotech Center in Monthey (Wallis) for production under GMP-conditions so that patients can be treated. »
Legacy Healthcare supports oncology care with plants
While cancer treatments contribute to saving lives, most cause side effects. The US National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) lists no fewer than 1,000 types. Patients’ quality of life is worsened and there is a long-term impact on survivors. Hence, oncology supportive care has become an integrated part of cancer care.
Addressing side effects
Side effects like hair loss and fatigue can be addressed. Botanical drugs, regulated by the FDA and EMA since 2004, originate from non-synthesised botanical extracts. Humans having co-evolved with plants, they are “recognised” in their natural state by the human body, making botanical drugs very safe in general. Botanical drugs are therefore more suitable for treating chronic issues, such as in oncology supportive care, compared to drugs with side effects.
Legacy Healthcare aspires to become the leader in botanical drug development, including for oncology supportive care. Its most advanced candidate is in Phase II/III. With a Chinese partner on board, it has started to explore the massive botanical drug leads potential Chinese medicine offers.
Accelerating the translation from the bench to the patient’s bedside
The recent burgeoning of immunotherapy research initiatives in Western Switzerland is spinning off new biotech startups and attracting established pharma companies. They are helping transitioning lab discoveries to the patients.
Incyte invests CHF 100 million in Yverdon
With 1,100 employees worldwide, Incyte, founded in Palo Alto in 1991, has great ambitions for the new sites of production it is setting in Y-Park in Yverdon-les-Bains . "80% of our business is in the field of cancer," says CEO Hervé Hoppenot. "We are currently witnessing a revolution in the treatment of cancer with immunology and the re-engineering of the immune system."
For him, this Swiss project is a sort of return. He worked for Novartis and chaired Novartis Oncology. Incyte's European headquarters is also located in Lausanne. And the American pharma has two clinical research groups in Lausanne and Geneva. "We wanted to keep the European headquarters and production site close enough," he says. "Y-Parc presented the most interesting option, being 20 minutes from Lausanne."
As of 2020, the future site will have a 3,500m2 production building with two bioreactors at the start and the possibility of six in the end. It is this building whose first stone was laid in September 2018. Next to this main building will be another building for administration and laboratories to control the manufacturing of the product, and a third for energy and consumables.
"Here in Yverdon we will have a plant for the production of monoclonal antibodies and the manufacture of the active ingredient," says Michael Morrissey, corporate senior vice president and head of global technical operations at Incyte. "Once it is manufactured, it will be shipped to other sites in Europe and the US to produce the treatments."
"We aim for 100% reliability for patients, both in efficiency and in the availability of the product. Criterion number one for us was therefore to find the skills to run a plant that will be able to achieve this level of reliability. We have found that in the heart of Switzerland in the canton of Vaud".
Novigenix combines blood test with AI for high-precision diagnostics
Intercepting colon cancer in its earliest stages and years before the appearance of symptoms could help eradicate the disease. From its offices at the Biopôle in Lausanne, Novigenix is developing non-invasive blood tests for early detection of cancer in collaboration with hospitals and clinics in Switzerland.
Its technology platform combines blood-based immuno-transcriptomics with advanced data analytics using machine learning and artificial intelligence (AI) to identify specific patterns of immune system reaction to cancer and its treatment. Changes in the gene expression profile of circulating immune cells that are exposed to tumours can be measured in blood and used as early indicators of cancer.
The first-generation test Colox for detection of colorectal cancer is currently available in Switzerland and a second generation is being developed on next-generation sequencing for global roll-out. Novigenix is also expanding the application of its technology platform to improve the monitoring of new cancer therapies such as immunotherapies.
Blood test for early detection of cancer
Lunaphore builds leadership in personalised immunotherapies
Lunaphore is a Swiss-based spin-off of the EPFL developing tissue staining devices for cancer diagnostics. It is recognized as one of the most innovative companies nationally and internationally.
Immunostainings are widely used biomarker tests which reveal presence of relevant cancer markers through coloration of tissue samples. Nowadays, techniques called multiplexing, allow testing several markers on the same sample to get a full understanding of how immune cells interact together against cancer. Immunophenotyping is key to understand each case and offer patients personalised therapies.
Lunaphore is developing a technology based on a microfluidic chip which aims to perform those tests much faster and with higher precision than standard techniques. Ultra-rapid multiplexing may enable same-day patient cases, with better outcomes. With its first product to be launched in the upcoming months, Lunaphore’s vision is to bring cutting-edge solutions to the tissue cancer diagnostics field.
Biopôle Lausanne: The campus where immunology scales up
A glimpse behind the community model that enables company development and inter-organisation collaboration and innovation.
By Nasri Nahas, CEO Biopôle SA
Shaping new products, designing new efficient immunotherapies, introducing nutritional goods into cancer research, these are just few of the inspiring converging business projects that visitors will find at Biopôle Lausanne and that attempt to foster research in life sciences and quickly concretise patients’ solutions.
At Biopôle Lausanne, life sciences companies and academic institutions cover, among other therapeutic focuses, the vast field of immunology, with an emphasis on vaccines, antibodies, cell therapies, and immune modulators. Leading companies include ADC Therapeutics, Anergis, Mymetics, Gnubiotics and Abionic. Though immuno-oncology represents an important research fields at Biopôle, our community members span their expertise across an impressive number of therapeutics areas and industries (pharma, biotech, medtech, digital-health), thus fostering increased exchange and cross-fertilisation of ideas. Furthermore, our corporate and academic members are increasingly aware of the need to play as a community to make the difference. Therefore, not only do they share costs like access to core facilities, technology platforms and discounted service offers, but they also do actively build synergies and long-lasting partnerships.
Access to potential business and research partners
One of the most important feature when establishing on campus and becoming a Biopôle Community Member is the access to the privileged network of industry and academic members of the community. This is naturally given by the proximity on site and by the participation in different scientific, business and social networking events organized to help the community to ever stay in touch. We like to think of our role at Biopôle SA as the enablers of these exchanges and we put a lot of efforts in constantly developing additional networking venues, programs and occasions to share and challenge research and business insights.
In 2018, two Biopôle companies in the field of immunology, Mymetics Corporation and Anergis SA, have entered into a Research Collaboration project: The pre-clinical study program, that is planned to last until end of 2019, will evaluate the immunogenicity profile of the Anergis peptides designed to treat birch allergy when presented on Mymetics’ proprietary virosomes, and will compare the results to Anergis’ AllerT product combination. This collaboration perfectly illustrates the community
spirit present at Biopôle Lausanne.
« Lausanne is the vibrant and growing « spot to be » for innovation in life sciences. »
How some companies at Biopôle Lausanne cover different immunology areas
Abionic develops a technology that uses the properties of adsorbed immunoglobulins to specifically recognize biomarkers present in a drop of blood in a nanofluidic setting.
Allergies / sepsis
ADC Therapeutics employs monoclonal antibodies specific to tumour antigens conjugated to a novel class of highly potent pyrroloben-zodiazepine (PBD) – based warheads to selectively kill cancer cells.
Anergis has developed a set of specific protein fragments that rapidly desensitizes the body towards allergens by efficiently down-regulating exaggerated immune response.
Allergies / sepsis
Ichnos Sciences develops bispecific antibodies that help immune cells to get in contact with cancer cells to better fight them. These antibodies are currently tested for breast cancer, myeloma and colorectal cancer.
Gnubiotics has developed a set of sugars that specifically feed the good bugs present in the gut while starving the bad ones, subsequently reinforcing the immune system.
Mymetics uses modified viral shells to stimulate the immune system without triggering infection as a novel vehicle for vaccination.