Treating Merkel cell cancer

MCC is a highly aggressive neuroendocrine cancer of the skin associated with the Merkel cell polyomavirus (MCPyV). Disease incidence has tripled over the past 20 years reaching 2 500 new cases per year within the EU. Evidence indicates that this is not only due to the ageing population but also due to a shift in the age distribution of the disease towards younger patients.

The EU-funded IMMOMEC (Immune modulating strategies for treatment of Merkel cell carcinoma) project is trying to establish an effective treatment for MCC based on immunotherapy. This therapy, which is being evaluated in a Phase II study in five different countries, combines the tumour-targeting human F16 monoclonal antibody fused to interleukin-2 (F16IL2) with paclitaxel, the frequently used cytotoxic agent in MCC treatment.

A better understanding of tumour biology and immunology has contributed towards major advances in cancer therapy. The IMMOMEC consortium has therefore developed techniques for analysing archived MCC tissue for specific biomarkers. A number of biomarkers correlating with systemic and tumour microenvironment-related immune responses have already been identified.

Furthermore, the consortium has established an open online registry for MCC patients. Analysis of the input data has demonstrated that the viral status of MCC is not associated with the clinical course of the disease. To ensure future exploitability of the MCC samples from the clinical trial, scientists have devised standard operating procedures for the collection, processing and storage of specimens.

For monitoring the outcome of the tumour-targeted delivery of the F16IL2 complex, immune dominant epitopes of MCC cancer cells were identified within the oncogenic proteins of MCPyV. These virus-reactive T cells were present in the blood of the majority of MCC patients and active against MCC cancer cells.

Collectively, the results of the IMMOMEC study will establish the clinical impact and determine the immunological effects of this novel immunotherapeutic approach. Long term this should improve patients’ prognosis and quality of life.