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IMmune MOdulating strategies for treatment of MErkel cell Carcinoma

Establishing new treatment methods for the Merkel cell carcinoma

11 Partners from 8 Countries

To date, there is no established therapy for the Merkel cell carcinoma (MCC), a rare but very aggressive form of skin cancer. This is especially discouraging because the incident rate is continually on the rise. The MCC has a high mortality rate and is one of the most fatal types of skin cancer. The goal of IMMOMEC (Immune MOdulating strategies for treatment of MErkel cell Carcinoma) is to test a new treatment method for MCC and to characterize it in detail. The European Commission-funded research project emphasizes the development of a particular immune therapy against this highly malignant

tumour. This large-scale project is coordinated by the Department of Dermatology and Venereology at the Medical University of Graz.The MCC is an especially immunogenic tumour: this is apparent, among other things, in that the tumour appears much more often in immunosuppressed patients, e.g. after organ transplantation or in patients with hematopoietic disorders. This is the exact point where the EU project IMMOMEC starts its research trying to find an innovative therapy for this type of skin cancer based on a specific activation of the immune system.

An international consortium is involved in working on this project, and stems from 8 countries. In addition to Austria, participants stem from Denmark, Germany, England, France, Italy, Spain and Poland. The team of high-ranking European researchers is led by Prof. Dr. Jürgen C. Becker, Department of Dermatology and Venereology at the Medical University of Graz.

“Our approach is based on the specific enrichment of the immunostimulatory T-cell growth factor interleukin 2 in the tumour tissue. For this purpose we use an antibody which recognizes the blood vessels of the tumour and docks there straight away. Interleukin 2 is coupled to this antibody and deploys directly at the tumour, fighting it this way’’, says project coordinator Jürgen C. Becker.

During immune therapy, a person’s immune system is influenced – in this case it is activated with the growth factor interleukin 2. Interleukin 2 is produced by a person’s own immune system and serves to strengthen immune responses, especially those of specific killer cells, namely T-cells. These specific immune responses are primarily involved in the control and resistance of tumour diseases. The treatment of the melanoma (black skin cancer) with conventional interleukin 2 is approved in the USA, for example, but is carried out only in a few centers worldwide, because a very high dosage of the

conventional interleukin 2 has to be administered. Only with these high, systematic dosages can the necessary concentration of the growth factor at the tumour be achieved, as they are needed for the immunostimulatory effect. Using the IMMOMEC-selected approach, much smaller amounts are needed, because the interleukin 2 is concentrated directly at the tumour. Consequently, the treatment is much better tolerated and more specific.

Not only is the clinical success of a tumour-directed, targeted interleukin 2-therapy for patients with advanced MCC being investigated in this EU project, the spontaneous and therapeutically strengthened immune responses are also being characterized in detail. Consequently, the MCC serves as a model tumour for other solid tumours and allows conclusions to be drawn about the relevance of immune therapy in cancer treatment in general. In this project, especially predictive and prognostic biomarkers will be established for the purpose of individual immunotherapy.

“We are trying to establish a new, effective immune therapy for Merkel cell carcinoma.” Jürgen Becker

Facts & Figures

What is the Merkel cell carcinoma?

Objectives Partner

www.immomec.eu

Coordinator IMMOMEC-ProjectUniv.-Prof. Dr. Dr. Jürgen C. BeckerDepartment of Dermatology and VenereologyMedical University of GrazAuenbruggerplatz 88036 Graz, AUSTRIAjuergen.becker@medunigraz.attel.: 0043 (0)316 / 385 72808

Total project volume: € 7.4MDuration: 4 yearsProject start: January 1, 2012Project partners: 9 academic facilities and 2 industry partners from 8 countriesGoals: Researching new immunological treatment methods for the Merkel cell carcinoma

The MCC is a very aggressive form of skin cancer. With an observed frequency of 0.44 cases per 100,000 people per year, it is actually quite rare, but incidences have increased alarmingly over the past 10 years. Mostly the elderly are affected with the average age of onset being over 70. The trend, however, shows that more people, and a greater number of younger people, are being diagnosed with this cancer.

1. Establish an effective therapy for Merkel cell carcinoma evaluated in a multicentre randomized clinical phase II trial

2. Establish the feasibility of effective immunotherapy for solid cancers

3. Identification and characterization of HLA-restricted immunodominant T cell epitopes specific for MCC to monitor the immune modulating effect and to develop specific therapeutics

4. Identification of prognostic and predictive biomarkers, i.e. search for markers foretelling

5. Establish a European network for research and therapy of MCC

• Medical University of Graz, Austria• Philogen S.p.A., Siena, Italy• immatics biotechnologies GmbH,

Tübingen, Germany• Herlev University, Copenhagen (Region

Hovedstaden, Hillerod), Denmark• Assistance Publique-Hôpitaux de Paris,

France• Fundació Privada Clínic per a la Recerca

Biomèdica, Spain• Charité – Medical University of Berlin,

Germany• University of Tübingen, Germany• The University of Nottingham, England• University Hospital Essen, Germany• Maria Skłodowska-Curie Memorial Cancer

Center and Institute of Oncology, Warsaw, Poland

Medical Univers i ty of Graz