CTL公司*
过继性细胞移植
CD8型
流式细胞术
黑色素瘤
细胞毒性T细胞
免疫学
T细胞
免疫分型
免疫疗法
生物
医学
癌症研究
分子生物学
抗原
体外
免疫系统
生物化学
作者
Norbert Meidenbauer,J. Marienhagen,Monika Laumer,Sandra Vogl,Jana Heymann,Reinhard Andreesen,Andréas Mackensen
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2003-02-15
卷期号:170 (4): 2161-2169
被引量:161
标识
DOI:10.4049/jimmunol.170.4.2161
摘要
Abstract Adoptive T cell therapy has been successfully used for treatment of viral and malignant diseases. However, little is known about the fate and trafficking of transferred Ag-specific T cells. Using the tetramer (TM) technology which allows for detection and quantification of Ag-specific CTL, we assessed the frequency of circulating Melan-A-specific CTL in advanced melanoma patients during adoptive T cell therapy. Melan-A-specific CTL were generated from HLA-A2.1+ patients by in vitro stimulation of CD8+ T cells with dendritic cells pulsed with a mutated HLA-A2-binding Melan-A (ELAGIGILTV) peptide. Eight patients received three infusions of 0.25–11 × 108 Melan-A-specific CTL i.v. at 2-wk intervals along with low-dose IL-2. The transferred T cell product contained a mean of 42.1% Melan-A-TM+ CTL. Before therapy, the frequencies of Melan-A-specific CTL in patients’ circulating CD8+ T cells ranged from 0.01 to 0.07%. Characterization of the TM frequencies before and at different time points after transfer revealed an increase of circulating Melan-A-specific CTL up to 2%, correlating well with the number of transferred CTL. An elevated frequency of TM+ T cells was demonstrated up to 14 days after transfer, suggesting long-term survival and/or proliferation of transferred CTL. Combining TM analysis with a flow cytometry-based cytokine secretion assay, unimpaired production of IFN-γ was demonstrated in vivo for at least 24 h after transfer. Indium-111 labeling of Melan-A-specific CTL demonstrated localization of transferred CTL to metastatic sites as early as 48 h after injection. Overall, the results suggest that in vitro-generated Melan-A-specific CTL survive intact in vivo for several weeks and localize preferentially to tumor.
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