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Cancer Immunotherapy, targets Survivin, and Establishment of Evaluation Methods of Therapeutic Effects

癌症免疫治疗、针对Survivin及疗效评价方法的建立

基本信息

批准号：
18591420
负责人：
TSURUMA Tetsuhuro
金额：
$ 2.57万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591420/
关键词：
cancer immunotherapy peptide pentide vaccine therapy survivin-2B IFN-a Tetramer staining ELISPOT assay MHCクラスI 評価

项目摘要

In this research, we established firm techniques of tetramer staining and ELTSPOT assay, which could monitor the survivin-2B peptide specific immunological responses. We made out that the vaccination using the surviving-2B peptide with IFA and IFN-a could efficiently induce the peptide specific immunological responses. However, the vaccination could not effectively induce the clinical responses, which have cytoreductive effects in most cases. In many cases which could not be induced the clinical responses, the MHC class I expression level was down-regulated in the primary focus. So, we concluded that the down-regulation of MHC class I expression level might be one of the reasons that the vaccination could not efficiently induce the clinical responses in despite of the induction of the peptide specific Ms. In addition, we investigated the relationship between the MHC class I expression level and the prognosis in cases that were operated in our hospitals. The survival rate of the cases that have the down-regulation of the MHC class I expression level was lower in comparison with the cases that do not have the down-regulation. So the MHC class I expression level might be the novel indication of malignant potential. In this research, we concluded that the most suitable indication of the peptide vaccine therapy might be low-grade cases that the MHC class I expression level was not down-regulated.

本研究建立了稳定的四聚体染色和ELTSPOT检测技术，可用于监测Survivin-2B肽特异性免疫反应。结果表明，用Survivin-2B肽与IFA和IFN-α联合免疫可有效地诱导肽特异性免疫应答。然而，疫苗接种不能有效地诱导临床应答，其在大多数情况下具有细胞减少作用。在许多不能诱导临床应答的病例中，原发灶中MHC I类表达水平下调。因此，我们得出结论，MHC I类表达水平的下调可能是疫苗接种不能有效地诱导临床反应的原因之一，尽管肽特异性Ms的诱导。此外，我们调查了MHC I类表达水平与预后之间的关系，在我院手术的病例。MHC I类表达水平下调的病例的存活率低于未下调的病例。因此，MHC I类分子表达水平可能是恶性潜能的新指标。在本研究中，我们得出结论，肽疫苗治疗的最合适的适应症可能是MHC I类表达水平未下调的低度病例。