Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells
Control of mesothelin-expressing ovarian cancer using adoptive transfer of mesothelin peptide-specific CD8+ T cells
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DOI：
10.1038/sj.gt.3302913
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发表时间：
2007-06-01
期刊：
影响因子：
5.1
通讯作者：
Wu, T-C
中科院分区：
文献类型：
--
作者：
Hung, C-F;Tsai, Y-C;Wu, T-C
靶向间皮素的癌症免疫疗法代表了用于控制卵巢癌的潜在合理方法，因为大多数卵巢癌表达高水平的间皮素。在当前的研究中，我们创建了表达间皮素阳性荧光素酶的卵巢癌模型MOSEC/ luc。这种表达荧光素酶的肿瘤模型允许我们使用非侵入性生物发光成像系统定量肿瘤攻击小鼠中的肿瘤分布和肿瘤负荷。此外，我们鉴定了由MOSEC/luc肿瘤细胞内源性加工和呈递的H-2D（B）限制性间皮素肽特异性细胞毒性T淋巴细胞（CTL）表位（氨基酸（aa）406-414）。我们发现间皮素肽（aa 406 -414）特异性CD 8（+）T细胞的过继转移导致MOSEC/luc肿瘤细胞的控制。MOSEC/luc肿瘤模型和新鉴定的H-2D（B）-限制性鼠间皮素特异性CTL表位（aa 406 -414）将对于卵巢癌的免疫疗法的开发以及对于定量CD 8（+）T细胞介导的免疫测定的开发非常有用。
Cancer immunotherapy targeting mesothelin represents a potentially plausible approach for the control of ovarian cancer as most ovarian cancers express high levels of mesothelin. In the current study, we created a mesothelin-positive luciferase- expressing ovarian cancer model, MOSEC/ luc. This luciferase- expressing tumor model allowed us to quantitate tumor distribution and tumor load in tumor-challenged mice using a non-invasive bioluminescence imaging system. In addition, we identified an H-2D(b)-restricted mesothelin peptide-specific cytotoxic T-lymphocyte ( CTL) epitope (amino acid (aa) 406-414) that was endogenously processed and presented by MOSEC/luc tumor cells. We showed that adoptive transfer of mesothelin peptide (aa406-414)- specific CD8(+) T cells led to the control of MOSEC/luc tumor cells. The MOSEC/luc tumor model and the newly identified H-2D(b)-restricted murine mesothelin- specific CTL epitope ( aa406-414) will be very useful for the development of immunotherapy for ovarian cancer as well as for the development of quantitative CD8(+) T cell-mediated immunological assays.