Immunotherapy for Myeloproliferative Neoplasms (MPN)

Susanne      Hofmann; Anna      Babiak; Jochen      Greiner

Abstract

The four major entities that form the group of myeloproliferative neoplasms (MPN) are BCR-ABL positive chronic myeloid leukaemia (CML), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET) and polycythemia vera (PV). All four are clonal diseases of the haematopoietic stem or precursor cell, they are of a chronic nature and potentially aggravate to myelofibrosis or transform into acute leukaemia. Several strategies are pursued in the treatment of MPN. On the one hand, targeted therapies such as tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) and JAK2-inhibitors are adopted in MPN as well as rather unspecific treatment with interferon-alpha and with the newer group of immunomodulatory drugs (IMIDs). On the other hand, cellular immunotherapeutical options as allogeneic haematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) are exerted in patients with MPN. Evidence resulting from graft-versus-leukaemia (GvL) effect was the key to develop more specific immunotherapies for patients with haematologic malignancies. In this context, CML is a model for immunotherapeutic approaches, and therefore, vaccination trials using peptides derived from leukaemia-associated antigens (LAA) to stimulate specific T cells are currently under investigation. But also in BCR-ABL-negative MPN, antigens have been identified and immunomodulatory treatment strategies have been performed. All of the current immunotherapeutical options in patients with MPN will be discussed throughout this review.

Keywords: Immunotherapy, vaccine, leukaemia-associated antigen (LAA), myeloproliferative neoplasms (MPN), CML, polycythemia, chronic idiopathic myelofibrosis, eosinophilic, hypereosinophilic syndrome, clonal diseases, Molecular Abnormalities, chromosome, mRNA, mastocytosis, platelet, growth factor, fusion gene, epitopes, T cell, Leukaemia, Antigens, T cells, humoral immune responses, tumour cell proliferation, cDNA, hydroxyurea, busulfan, proliferation, peptide vaccination, cytokine production, dose-dependent, cytoplasm, fusion, amino acid substitutionstions, subcutaneously, immune responses, hyaluronic acid, Heat shock proteins (HSPs), monotherapy, intradermal injection, Dendritic Cell Immunotherapy, toxicity, receptors