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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
MGBG in Combined Anticancer Chemotherapy
Letters in Drug Design & Discovery Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Advances in the Management of Malignant Hemopathies: The Role of Statins
Recent Patents on DNA & Gene Sequences Characterization of Molecular and Functional Alterations of Tumor Endothelial Cells to Design Anti-Angiogenic Strategies
Current Vascular Pharmacology Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012
Current Topics in Medicinal Chemistry Synthesis and Enzymological Characterization of Some 2-(Substitutedphenylamino) quinazolin-4(3H)-one Derivatives as Potent α-Glucosidase Inhibitors In Vitro
Letters in Drug Design & Discovery Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases
Current Gene Therapy The Use of Structural Biology in Janus Kinase Targeted Drug Discovery
Current Drug Targets Radiolabelled Regulatory Peptides for Imaging and Therapy
Anti-Cancer Agents in Medicinal Chemistry Cancer Stem Cells in Pediatric Brain Tumors
Current Stem Cell Research & Therapy Lipoidal-Nano Architecture for Parental Drug Delivery: Formulation Development and Regulatory Concerns
Current Applied Polymer Science Ribozyme- and Deoxyribozyme-Strategies for Medical Applications
Current Drug Targets Pyrrolo[2,1-c][1,4]benzodiazepine as a Scaffold for the Design and Synthesis of Anti- Tumour Drugs
Anti-Cancer Agents in Medicinal Chemistry IAPs as a Target for Anticancer Therapy
Current Cancer Drug Targets Editorial [Hot topic: The Urokinase Receptor System as Strategic Therapeutic Target: Challenges for the 21st Century (Executive Guest Editor: Bernard Degryse)]
Current Pharmaceutical Design Foamy Virus Vectors: An Awaited Alternative to Gammaretro- and Lentiviral Vectors
Current Gene Therapy Mechanism-based Combinations with Pim Kinase Inhibitors in Cancer Treatments
Current Pharmaceutical Design Novel Immunotherapies for Hematological Malignancies
Current Molecular Pharmacology Anionic Host Defence Peptides from the Plant Kingdom: Their Anticancer Activity and Mechanisms of Action
Protein & Peptide Letters