Abstract
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.
Current Cancer Drug Targets
Title:Advances in Immunotherapy of Chronic Myeloid Leukemia CML
Volume: 13 Issue: 7
Author(s): Stefanie Andrea Erika Held, Annkristin Heine, Karin Tina Mayer, Mario Kapelle, Dominik Georg Friedrich Wolf and Peter Brossart
Affiliation:
Keywords: Chronic myeloid leukemia, immunotherapy, leukemia associated antigens.
Abstract: 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.
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Cite this article as:
Erika Held Andrea Stefanie, Heine Annkristin, Mayer Tina Karin, Kapelle Mario, Friedrich Wolf Georg Dominik and Brossart Peter, Advances in Immunotherapy of Chronic Myeloid Leukemia CML, Current Cancer Drug Targets 2013; 13 (7) . https://dx.doi.org/10.2174/15680096113139990086
DOI https://dx.doi.org/10.2174/15680096113139990086 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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