用于慢性粒细胞白血病疫苗接种的Bcr/abl+自体树突状细胞

Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.

作者信息

Westermann J, Kopp J, Körner I, Richter G, Qin Z, Blankenstein T, Dörken B, Pezzutto A

机构信息

Dept of Hematology, Oncology and Tumorimmunology, Robert Rössle Klinik, Charité, Humboldt University, Berlin, Germany.

出版信息

Bone Marrow Transplant. 2000 May;25 Suppl 2:S46-9. doi: 10.1038/sj.bmt.1702354.

DOI:10.1038/sj.bmt.1702354

PMID:10933188

Abstract

In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl+ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin-, CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c. vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC-based vaccination strategies are a promising clinical approach, particularly as postremission immunotherapy in the setting of autologous stem cell transplantation.

摘要

在慢性粒细胞白血病（CML）中，体外生成的树突状细胞（DC）的特征是组成性表达bcr/abl以及可能其他尚未明确的白血病相关抗原，因为这些DC与白血病细胞有共同的祖细胞。体外已描述了抗白血病T细胞反应的诱导。在一项I期疫苗接种研究中，在良好生产规范（GMP）条件下，主要从慢性期CML患者的单核细胞前体生成自体bcr/abl+ DC。可以产生足够数量的Lin-、CD80+、CD86+、CD83+、DR+ DC用于皮下接种1×10⁶ - 5×10⁷个DC。使用单核细胞前体，每接种的外周血单个核细胞（PBMC）中DC的产量在1% - 6%范围内。此外，我们可以在体外证明，通过用编码白细胞介素-7的基因进行逆转录病毒转导，CD34⁺来源的DC的T细胞刺激能力可增强2 - 3倍。基于DC的疫苗接种策略是一种有前景的临床方法，特别是作为自体干细胞移植缓解后的免疫治疗。