Adoptive transfer of neoantigen-specific T-cell therapy is feasible in older patients with higher-risk myelodysplastic syndrome
Adoptive transfer of neoantigen-specific T-cell therapy is feasible in older patients with higher-risk myelodysplastic syndrome
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DOI：
10.1016/j.jcyt.2020.11.003
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发表时间：
2021-02-18
期刊：
影响因子：
4.5
通讯作者：
Bejar, Rafael
中科院分区：
文献类型：
--
作者：
Tanaka, Tiffany N.;Ferrari, Valentina;Bejar, Rafael
背景：骨髓增生异常综合征(MDS)是成人获得性骨髓衰竭中最常见的类型，以髓系前体细胞不能有效成熟和外周血细胞减少为特征，并伴有较高的感染、出血和输血依赖。对于高危MDS患者，在标准的低甲基化药物(HMA)治疗后复发或无反应，2年生存率为15%。方法：作者报道了一种名为个性化过继细胞疗法的新型实验性T细胞疗法的可行性和安全性，该疗法针对MDS特异性突变选择、免疫和扩增T细胞，并针对患者特定的肿瘤细胞新抗原。体细胞突变是包括MDS在内的癌症的致病因素，因为这些变革性的基因突变可能产生新的免疫原性蛋白(即新肽和可能的新抗原)，这些蛋白可能是靶向治疗的。结果：作者证明了适应性免疫系统可以在体外培养识别新肽为新抗原，并且培养的输注扩大了，到目前为止，新抗原免疫的自体T细胞在三名接受治疗的患者中是可行和安全的。讨论：作者报告了他们的第一个人类第一阶段临床试验的早期结果，该临床试验旨在评估这种新形式的过继T细胞免疫疗法对HMA难治性高危MDS患者的安全性和耐受性。(C)2020年国际细胞与基因治疗学会。爱思唯尔公司出版，版权所有。
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.