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NATURE:针对新诊断的胶质母细胞瘤进行积极个性化的疫苗接种试验

2018-12-22 海北 MedSci原创

目前,胶质母细胞瘤患者尚未充分受益于最近大热的检查点抑制剂等癌症治疗方面的突破。对于使用检查点抑制剂成功的治疗,高突变负荷和对新表位的反应被认为是必不可少的。

目前,胶质母细胞瘤患者尚未充分受益于最近大热的检查点抑制剂等癌症治疗方面的突破。对于使用检查点抑制剂成功的治疗,高突变负荷和对新表位的反应被认为是必不可少的。胶质母细胞瘤中免疫细胞的肿瘤内浸润有限,这些肿瘤仅含有30-50个非同义突变。利用肿瘤抗原的完整全集 - 即未突变的抗原和新表位 - 可以提供更有效的免疫疗法,尤其是对于具有低突变负荷的肿瘤。
最近,在胶质瘤主动个性化疫苗联盟(GAPVAC)的I期试验GAPVAC-101中,研究人员将高度个性化的疫苗接种与两种类型的肿瘤抗原整合到标准治疗中,以最佳地利用新诊断的胶质母细胞瘤患者的有限目标空间。
15例患有人白细胞抗原(HLA)-A * 02:01或HLA-A * 24:02阳性的胶质母细胞瘤患者用来自预制的未突变抗原文库的疫苗(APVAC1)进行治疗,然后用APVAC2治疗,优先治疗有针对性的新表位。个性化基于个体肿瘤的转录组和免疫肽的突变和分析。
GAPVAC方法是可行的,并且具有聚-ICLC(多核糖核苷 - 多聚胞苷酸 - 聚-L-赖氨酸羧甲基纤维素)和粒细胞-巨噬细胞集落刺激因子作为佐剂的疫苗显示出有利的安全性和强免疫原性。未突变的APVAC1抗原引发中枢记忆CD8+ T细胞的持续反应。APVAC2主要诱导T辅助细胞1型对抗预测的新表位的CD4+ T细胞应答。

原始出处
Hilf N et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. NATURE 2018, DOI: 10.1038/s41586-018-0810-y.

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    2019-06-09 rgjl
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    2019-10-08 liye789132251
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