KRAS G12V新抗原特异性T细胞受体用于针对瘤的采用性T细胞治疗
Dan Lu1,2,3, Yuan Chen1,2,4, Min Jiang1,2
1CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Nature communications
|October 12, 2023
概括
研究人员确定了针对KRAS-G12V突变新抗原的T细胞受体 (TCR). 这些TCR-T细胞表现出抗瘤活性,突出了它们在癌症免疫治疗中的潜力.
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:
- 克拉斯突变是各种癌症的关键驱动因素,是重要的治疗点.
- T细胞受体 (TCR) 可以识别由人类淋巴细胞抗原 (HLA) 分子呈现的瘤特异性新抗原,从而实现向癌症免疫治疗.
研究的目的:
- 为了识别和描述KRAS-G12V突变新抗原的特异性TCR,由HLA-A*11:01.1呈现.
- 在临床前模型中评估针对KRAS-G12V的工程TCR-T细胞的抗瘤疗效.
主要方法:
- 在HLA-A*11:01.的背景下,鉴定KRAS-G12V 9-mer新抗原特异性的TCRs.
- 构建和体外特征的TCR-T细胞,评估细胞因子分泌和细胞毒性对KRAS-G12V表达瘤细胞.
- 在临床前小鼠模型中评估TCR-T细胞的抗瘤活性.
主要成果:
- 通过HLA-A*11:01所呈现的KRAS-G12V9米尔新抗原特异的两个TCR被确定.
- 改造的TCR-T细胞表现出针对KRAS-G12V突变瘤细胞的特定细胞因子分泌和细胞毒性.
- 临床前研究表明,TCR-T细胞在小鼠模型中具有抗瘤活性.
- 结构分析显示,与野生型和较长的相比,KRAS-G12V突变的形状不同,这对于TCR识别至关重要.
结论:
- 该研究确定了具有治疗潜力的新型TCRs,用于KRAS-G12V突变癌症.
- 了解TCR--HLA相互作用机制为开发有效的基于TCR的免疫疗法提供了洞察力.
- 这些TCR显示出显著的抗瘤疗效,支持其在治疗KRAS突变瘤的临床应用方面的进展.
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