血液系统恶性肿瘤患者的基于树突状细胞的疫苗

Dendritic cell-based vaccines in patients with hematological malignancies.

作者信息

Brugger W, Schneider A, Schammann T, Dill P, Grünebach F, Bühring H J, Kanz L, Brossart P

机构信息

University of Tübingen, Medical Center, Dept. of Hematology, Oncology, Immunology, and Rheumatology, Otfried-Müller Str. 10, 72076 Tübingen, Germany.

出版信息

Ann N Y Acad Sci. 2001 Jun;938:359-62; discussion 362-3. doi: 10.1111/j.1749-6632.2001.tb03603.x.

DOI:10.1111/j.1749-6632.2001.tb03603.x

PMID:11458523

Abstract

The epithelial mucin MUC1 is overexpressed on many epithelial malignancies as well as on some B-cell lymphomas and multiple myelomas. In the present study, we described MUC1 expression also on primary AML blasts. To analyze the presentation of MUC1-derived HLA-A2 restricted peptides by primary AML blasts, we induced MUC1-specific cytotoxic T-lymphocytes (CTLs) in vitro using peptide pulsed dendritic cells from HLA-A2+ healthy donors as antigen-presenting cells. These CTLs efficiently lysed primary AML blasts that constitutively expressed both MUC1 and HLA-A2. The specificity of the CTLs was confirmed in a cold target inhibition assay. Our data demonstrate that MUC1-derived peptides are tumor antigens in AML which could potentially be used for immunotherapeutic approaches.

摘要

上皮粘蛋白MUC1在许多上皮恶性肿瘤以及一些B细胞淋巴瘤和多发性骨髓瘤中过表达。在本研究中，我们还描述了MUC1在原发性急性髓系白血病（AML）原始细胞上的表达。为了分析原发性AML原始细胞对MUC1衍生的HLA - A2限制性肽的呈递情况，我们使用来自HLA - A2 +健康供体的肽脉冲树突状细胞作为抗原呈递细胞，在体外诱导产生MUC1特异性细胞毒性T淋巴细胞（CTL）。这些CTL有效地裂解了组成性表达MUC1和HLA - A2的原发性AML原始细胞。在冷靶抑制试验中证实了CTL的特异性。我们的数据表明，MUC1衍生的肽是AML中的肿瘤抗原，有可能用于免疫治疗方法。