ABBV-184:一种新的生存特异性TCR/CD3双特异性T细胞激活剂,对固体瘤和血液恶性瘤都具有活性
Adam S Chervin1, Jennifer D Stone1, Iwona Konieczna1
1AbbVie Inc., North Chicago, Illinois.
Molecular cancer therapeutics
|June 9, 2023
概括
一种新的T细胞激活剂,ABBV-184,向瘤上的细胞内幸存. 这种双特异性疗法激活T细胞,有效地杀死急性髓性白血病和非小细胞肺癌中的癌细胞.
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:
- CD3双特异性T细胞参与剂 (TCE) 将T细胞重定向杀死瘤细胞.
- 许多瘤抗原是细胞内的,不能被基于抗体的TCE接收.
- T细胞受体 (TCR) 识别由MHC分子呈现的细胞内.
研究的目的:
- 描述ABBV-184的临床前评估,一种新的TCR/抗CD3双特异分子.
- 评估ABBV-184在向癌细胞上的幸存/MHC复合物的疗效.
主要方法:
- ABBV-184包括一种可溶性TCR,向一种幸存者衍生的/HLA-A*02:01复合物和一种抗CD3结合剂.
- 临床前评估涉及体外和体内研究,使用癌细胞系和来自患者的样本.
主要成果:
- ABBV-184显示出强大的T细胞激活,增殖和细胞毒性对抗HLA-A2阳性癌细胞.
- 在急性髓性白血病 (AML) 和非小细胞肺癌 (NSCLC) 模型中观察到有效的向.
- 这种双特异性分子即使对低密度/MHC标也表现出有效性.
结论:
- ABBV-184是治疗AML和NSCLC的有希望的临床候选者.
- 基于TCR的双特异性药物提供了一种针对细胞内抗原的策略.
- 由于ABBV-184能够准幸存者的能力,它具有广泛的治疗潜力.
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