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一种针对黑色素瘤患者的免疫性个人新抗原疫苗

Patrick A Ott^1,2,3, Zhuting Hu¹, Derin B Keskin^1,3,4

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

|July 6, 2017

概括

个性化新抗原疫苗在癌症患者中显示安全性和免疫性. 这种方法扩大了T细胞对瘤的反应,在与免疫治疗相结合时导致了持久的缓解和增强的反应.

科学领域:

免疫学
癌症学
疫苗开发

背景情况:

有效的抗瘤免疫依赖于向癌症新抗原的T细胞,
新抗原具有高度免疫性,因为它们不在正常组织中,绕过了中央耐受性.
测序和机器学习的进步使HLA结合的系统发现和预测成为可能.

研究的目的:

证明个性化新抗原疫苗的可行性,安全性和免疫性.
评估疫苗能够扩大现有的T细胞群并诱导新的新抗原特异性T细胞群.
评估疫苗对单独或与其他疗法结合的瘤控制和患者结果的影响.

主要方法:

开发和使用针对20种预测的个人瘤新抗原的疫苗.
针对突变新抗原的疫苗诱导的多功能CD4+和CD8+T细胞反应的分析.
监测患者的结果,包括瘤复发和随后的抗PD-1治疗反应.

主要成果:

疫苗诱导的T细胞向了显著比例的独特新抗原 (60% CD4+,16% CD8+).
这些T细胞特别识别了突变的新抗原,而不是野生类型的,在某些情况下,是自身的瘤.
在6名接种疫苗的患者中,有4名在25个月内没有复发;两名复发患者通过抗PD-1治疗和扩大新抗原特异性T细胞实现了完全回归.

结论:

在癌症患者中,个性化新抗原疫苗接种是可行的,安全的和免疫的.
疫苗引起强大的T细胞反应,可以向瘤,并有助于临床效益.
这种方法作为单独的治疗或与检查点抑制剂结合来增强瘤控制具有前景.

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