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一种针对突变IDH1的疫苗诱导了抗瘤免疫力

Theresa Schumacher¹, Lukas Bunse¹, Stefan Pusch²

¹1] Department of Neurooncology, University Hospital Heidelberg and National Center for Tumor Diseases, 69120 Heidelberg, Germany [2] German Cancer Consortium (DKTK) Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [3].

|July 22, 2014

概括

异酸脱酶1型 (IDH1) 中的突变驱动着质瘤的发展. 用疫苗向IDH1 (R132H) 突变显示出针对这些瘤的新免疫疗法策略的希望.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

异酸脱酶1型 (IDH1) 的单点突变是质瘤发展的早期事件.
这些突变,特别是IDH1(R132H),产生一种新型酶功能,产生甲基代谢物2 - 基酸盐 (2-HG).
IDH1 ((R132H) 存在于超过70%的II级和III级扩散性质瘤中,代表了瘤特异性的新抗原.

研究的目的:

为了研究IDH1 (R132H) 突变的免疫性,开发一种突变特异性疫苗.
评估IDH1 ((R132H) 作为癌症免疫治疗的标的潜力.

主要方法:

对MHCII类分子上的体呈现的分析.
诱导CD4的T-助手-1 (TH1) 反应.
患者自发免疫反应的评估.
在人类MHC的小鼠模型中进行类疫苗接种.

主要成果:

来自突变的IDH1 ((R132H) 区域的酸在MHCII类中呈现.
诱导突变特异的CD4 (((+) TH1反应和抗体.
患者的T细胞和抗体对IDH1 (R132H) 的自发免疫识别.
用IDH1 (R132H) 接种疫苗会引起抗瘤免疫力,并控制小鼠的瘤生长.

结论:

IDH1 ((R132H) 含有适用于突变特异性疫苗接种的免疫原性表位.
CD4(+) 可以产生T细胞依赖的抗瘤免疫力来对抗IDH1(R132H).
一种针对突变的抗IDH1 (R132H) 疫苗是IDH1 (R132H) 突变结质瘤的潜在治疗策略.

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