Tyrosine kinase inhibitors induce sustained disease remissions in chronic myeloid leukemia by exploiting the
addiction of this type of leukemia to the activity of the fusion oncogene BCR-ABL. However, these agents fail to
eradicate CML stem cells which are ultimately responsible for disease relapses upon treatment discontinuation. Evidence
that the immune system can effectively reject CML stem cells potentially leading to patient cure is provided by the
experience with patients receiving allogeneic bone marrow transplantations. Compelling evidence indicates that more
modern, antigen-specific immunotherapeutic approaches are also feasible and hold strong potential to be clinically
effective. Amongst these, particularly promising is the use of autologous dendritic cells pulsed with antigens or direct
application of in vitro transcribed RNA encoding for leukemia-associated antigens, since this approach allows to
circumvent HLA-restriction of the leukemia-associated T cell epitopes that have been eventually identified. Combining
these strategies with monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1, may help to obtain even stronger immune
responses and better clinical results. This narrative review addresses this topic by focusing in particular on the cell-based
immunotherapeutic strategies for CML and on the issue of the leukemia-associated antigens to be selected for targeting.
Keywords: Chronic myeloid leukemia, immunotherapy, leukemia associated antigens.
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