Chronic myeloid leukaemia (CML) is a disease of the haemopoietic stem cell, arising from a translocation t(9;22)(q34;q11). This translocation gives rise to a Philadelphia chromosome together with a BCR-ABL fusion gene that codes for a fusion protein with greatly enhanced tyrosine kinase activity. CML is a paradigm for the use of immunotherapy as well as being a model disease for the use of molecularly targeted therapies (tyrosine kinase inhibitors-TKI) in malignant disease. In patients with newly diagnosed chronic-phase CML, treatment with TKI results in a high rate of durable complete cytogenetic responses (CcyR), but 15% of patients never achieve a CCyR and a further 15-20% of patients achieve a CCyR but subsequently lose it. Moreover in the majority of patients who do respond well, BCR-ABL transcripts can still be detected in the blood and marrow for many years. These and others lines of evidence suggest that leukaemia stem cells persist in all or almost all patients and could pose a risk for relapse after many years of apparently successful treatment. In this study we propose to exploit this status of ‘minimal residual disease’ achieved with TKI by using a multi-epitope vaccine approach to eliminate all persisting leukaemia. Furthermore, we will investigate if the addition of immunomodulatory agents such as interferon-alpha will further enhance this vaccine-induced immune effect.
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