Adoptive Transfer Of Neoantigen-Specific T-Cell Therapy Is Feasible In Older Patients With Higher-Risk Myelodysplastic Syndrome
CYTOTHERAPY(2021)
摘要
Background: Myelodysplastic syndromes (MDS) represent the most common type of acquired bone marrow failure in adults and is characterized by ineffective maturation of myeloid precursor cells and peripheral cytopenias associated with higher rates of infection, bleeding and transfusion dependence. In higher-risk patients with MDS who relapse or do not respond after standard hypomethylating agent (HMA) therapy, the 2-year survival rate is 15%.Methods: Here the authors report the feasibility and safety of a novel experimental T-cell therapy called personalized adoptive cell therapy, which selects, immunizes and expands T cells against MDS-specific mutations and is targeted to patient-specific tumor cell neo-antigens. Somatic mutations serve as the pathogenic drivers of cancer, including MDS, as these transformative genetic mutations may generate novel immunogenic proteins (i.e., neopeptides and possible neoantigens) that may be targeted therapeutically.Results: The authors demonstrate that the adaptive immune system can be trained ex vivo to recognize neopeptides as neoantigens and that the infusion of culture-expanded, neo-antigen-immunized autologous T cells has been feasible and safe in the three patients treated to date.Discussion: The authors report on early results from their first-in-human phase 1 clinical trial that aims to assess the safety and tolerability of this novel form of adoptive T-cell immunotherapy for HMA-refractory patients with higher-risk MDS. (C) 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
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关键词
Myelodysplastic Syndromes, T cell therapy, Immunotherapy, Neoantigens
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