针对来自常见TP53突变的新抗原
Emily Han-Chung Hsiue1,2,3, Katharine M Wright2,4,5, Jacqueline Douglass1,2,3
1Ludwig Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Science (New York, N.Y.)
|March 2, 2021
概括
研究人员开发了一种针对常见TP53 (瘤蛋白p53) 突变R175H的新型抗体. 这种抗体有效地激活T细胞以破坏具有这种特定突变的癌细胞.
科学领域:
- 免疫学
- 癌症学
- 结构生物学
背景情况:
- TP53 (瘤蛋白p53) 是最常发生突变的癌症驱动基因.
- 针对突变的瘤抑制基因,包括TP53,由于缺乏可用的药物,在癌症治疗中仍然是一个重大挑战.
研究的目的:
- 在细胞表面发现常见TP53R175H突变的高度特异性抗体.
- 开发基于这种抗体的免疫治疗药物, 针对难以治疗的癌症.
主要方法:
- 对TP53 R175H突变具有高特异性的抗体与人白细胞抗原A (HLA-A) 的复合体的鉴定.
- 阐明抗体特异性的结构基础.
- 将抗体转化为两种单链抗体, 用于治疗.
- 在体外和体内 (小鼠) 测试两种特异性抗体在激活T细胞和溶解癌细胞中的有效性.
主要成果:
- 鉴定出一种在癌细胞上呈现的TP53 R175H新抗原的抗体.
- 即使在低复杂密度下,双特异单链diabody也有效地激活T细胞以溶解具有目标新抗原的癌细胞.
- 免疫治疗方法在体外和体外的有效性.
结论:
- 一种针对常见TP53 R175H突变的新型双特异抗体已经开发出来.
- 这种方法对传统难以向的突变癌症具有前景.
- 这种策略为癌症免疫治疗提供了潜在的新途径.
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