A phase I/IIa clinical trial of immunotherapy for elderly patients with acute myeloid leukaemia using dendritic cells co-pulsed with WT1 peptide and zoledronate

Department of Hematology and Oncology Center for Cell and Molecular Therapy Department of Clinical Laboratory, Kyoto University Hospital, Kyoto Medinet Medical Institute, MEDINET, Co., Ltd., Yokohama Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan. E-mail: .
British Journal of Haematology (Impact Factor: 4.71). 06/2011; 153(6):796-9. DOI: 10.1111/j.1365-2141.2010.08490.x
Source: PubMed
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    • "However, DLI provokes unmanageable graft-versus-host disease (GVHD) because many allogeneic antigens are targeted by donor T cells [2]. Leukemic antigen-specific autologous dendritic cell (DC)-based vaccination for hematological malignancies is currently explored to avoid off-target effects [3] [4]. The autologous DC therapy requires the production of DC vaccines from patient-derived peripheral blood mononuclear cells (PBMCs) through the use of leukapheresis. "
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    ABSTRACT: A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Dec 2014 · Cytotherapy
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    • "WT1-and hTERT-specific CD8+ T cell responses were observed in an HLA-A * 2402-positive patient, indicating cross-priming in vivo. In another study, we administered MoDCs pulsed with an HLA-A * 2402-restricted modified WT1 peptide that has higher affinity to the HLA molecule than the natural peptide to 3 patients [37]. We observed immune responses in 2 patients who exhibited transient disease stabilization. "
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    ABSTRACT: Relapse after chemotherapy is inevitable in the majority of patients with acute myeloid leukemia (AML). Thus, it is necessary to develop novel therapies that have different antileukemic mechanisms. Recent advances in immunology and identification of promising leukemia-associated antigens open the possibilities for eradicating minimal residual diseases by antigen-specific immunotherapy after chemotherapy. Several methods have been pursued as immunotherapies for AML: peptide vaccines, granulocyte-macrophage colony-stimulating factor-secreting tumor vaccines, dendritic cell vaccines, and adoptive T cell therapy. Whereas immunogenicity and clinical outcomes are improving in these trials, severe adverse events were observed in highly avid engineered T cell therapies, indicating the importance of the balance between effectiveness and side effects in advanced immunotherapy. Such progress in inducing antitumor immune responses, together with strategies to attenuate immunosuppressive factors, will establish immunotherapy as an important armament to combat AML.
    Preview · Article · Oct 2011 · Clinical and Developmental Immunology
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    ABSTRACT: The recent Food and Drug Administration (FDA) approval of a cellular therapy to treat castration resistant prostate cancer has reinforced the potential of cellular therapy to consolidate current pharmacological approaches to treating cancer. The emergence of the cell manufacturing facility to facilitate clinical translation of these new methodologies allows greater access to these novel therapies. Here we review different strategies currently being explored to treat haematological malignancies with a focus on adoptive allogeneic or autologous transfer of antigen specific T cells, NK cells or dendritic cells. These approaches all aim to generate immunological responses against overexpressed tissue antigens, mismatched minor histocompatability antigens or tumour associated antigens. Current successes and limitations of these different approaches will be discussed with an emphasis on challenges encountered in generating long term engraftment, antigen selection and implementation as well as therapeutic immune monitoring of clinical responses, with examples from recent clinical trials.
    Full-text · Article · Sep 2011 · Pathology
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