Immunotherapy against Merkel cell cancer
MCC is a highly aggressive and often lethal neuroendocrine cancer of the skin, associated with the recently discovered common Merkel cell polyomavirus (MCPyV) or with chronic UV exposure. Epidemiologic data indicate that there are approximately 2 500 new MCC cases per year within the EU and approximately 1000 of these patients will die from this disease. Albeit less common than melanoma, metastatic MCC is considered the most lethal form of skin cancer. Until recently, treatment of MCC patients was solely based on anecdotal observations, indicating the complete lack of evidence-based decisions. Several lines of evidence support MCC immunogenicity, indicating the potential of immune-modulating treatment strategies. With this in mind, scientists of the EU-funded IMMOMEC(opens in new window) (Immune modulating strategies for treatment of Merkel cell carcinoma) project investigated the safety and efficacy of an innovative immunotherapy involving the targeted delivery of interleukin-2 to the tumour microenvironment. Targeting of interleukin-2 was mediated through conjugation with a tenascin C antibody F16-IL2. At the same time, partners established new tools to monitor patients receiving immune modulating therapies in MCC alongside prognostic and predictive biomarkers. They identified MCC-specific T-cell epitopes and characterised specific T-cell responses using peripheral blood lymphocytes from patients across Europe. In addition, they investigated the mechanisms by which MCC evades immune response and studied the tumour inflammatory infiltrate both at a morphological and molecular level. Interestingly, preliminary data from the MCC registry created within IMMOMEC suggested that besides an increasing incidence, the age distribution of patients is slowly shifting towards younger patients. In addition, the viral status of MCC doesn’t seem to be associated with the clinical course of the disease. Overall, the comprehensive IMMOMEC translational research programme led to novel immune-monitoring techniques that could be used to analyse localised immune responses in the microenvironment of a variety of cancers. With respect to therapy, although the recruited number of patients did not result in significant clinical trial results, the project findings on MCC biology and immunology are expected to assist personalised therapy and improve the lifespan and quality of life of patients.
