Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients
Rare naturally occurring immune responses to three epitopes from the widely expressed tumour antigens hTERT and CYP1B1 in multiple myeloma patients
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DOI：
10.1111/j.1365-2249.2005.02879.x
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发表时间：
2005-09-01
影响因子：
4.6
通讯作者：
Schultze, JL
中科院分区：
文献类型：
--
作者：
Maecker, B;von Bergwelt-Baildon, MS;Schultze, JL
广泛表达的肿瘤抗原hTERT和CYP 1B 1通常在多发性骨髓瘤（MM）细胞中表达。已经启动了几项通过免疫疗法靶向这些抗原的试验。本研究的目的是探讨MM患者是否对最近鉴定的hTERT和CYP 1B 1表位有内源性预先存在的免疫应答。采用MHC四聚体检测和短期离体扩增方法，对27例不同疾病阶段的HLA-A * 0201（+）多发性骨髓瘤患者和20例健康HLA-A*0201（+）供体的外周血T细胞进行富集，并研究hTERT和CYP 1B 1特异性细胞毒性T细胞的存在。当细胞用含有优势hTERT衍生表位或两种CYP 1B 1衍生肽的四聚体染色时，在MM患者或健康对照的外周血中均未检测到四聚体阳性细胞的显著扩增。一个单一的离体肽刺激导致检测的hTERT特异性细胞的一个小群体（0.3-0.5%）的27例MM患者中的两个。没有患者或对照组显示出显着的CYP 1B 1特异性细胞扩增后，一个单一的肽刺激。因此，T细胞针对hTERT和CYP 1B 1的内源性体内致敏在MM患者中是罕见事件。这些结果表明，靶向hTERT和CYP 1B 1的策略可能必须利用技术来诱导T细胞应答。
The widely expressed tumour antigens hTERT and CYP1B1 are commonly expressed in multiple myeloma (MM) cells. Several trials targeting these antigens by immunotherapy have been initiated. The aim of this study was to explore whether patients with MM have an endogenous pre-existing immune response against recently identified epitopes from hTERT and CYP1B1. Peripheral blood T cells from 27 HLA-A*0201(+) multiple myeloma patients at different stages of disease and 20 healthy HLA-A*0201(+) donors were enriched and studied for the presence of hTERT- and CYP1B1-specific cytotoxic T cells using MHC tetramer detection and short-term ex vivo expansion. No significant expansion of tetramer-positive cells was detected in the peripheral blood of either MM patients or healthy controls when cells were stained with tetramers containing the dominant hTERT-derived epitope or two peptides derived from CYP1B1. A single ex vivo peptide stimulation led to the detection of a small population (0.3-0.5%) of hTERT-specific cells in two of 27 patients with MM. None of the patients or controls showed significant expansion of CYP1B1-specific cells after a single peptide stimulation. Thus, endogenous in vivo priming of T cells against hTERT and CYP1B1 is a rare event in MM patients. These results suggest that strategies targeting hTERT and CYP1B1 may have to utilize techniques to induce T cell responses from a naive precursor frequency.