在癌症中参与T细胞的双特异性抗体
Niels W C J van de Donk1, Sonja Zweegman1
1Amsterdam University Medical Centres, Vrije Universiteit Amsterdam, Department of Hematology, Amsterdam, Netherlands; Cancer Center Amsterdam, Amsterdam, Netherlands.
Lancet (London, England)
|June 4, 2023
概括
参与T细胞的双特异性抗体 (BsAbs) 将T细胞重定向以消除癌细胞. 虽然在血液癌症中有效,但固体瘤的进展受到目标特异性的限制,尽管皮膜黑色素瘤显示出有前途.
科学领域:
- 免疫学
- 癌症学
- 药理学
背景情况:
- 通过将T细胞与瘤细胞结合,T细胞参与的双特异性抗体 (BsAbs) 控制免疫系统.
- 在针对CD19,CD20,BCMA和GPRC5D等抗原的血液恶性瘤中,BsAbs已经显示出有效性.
- 固体瘤的挑战包括识别瘤特异性点,以尽量减少瘤外的毒性.
研究的目的:
- 审查T细胞参与双特异性抗体在癌症治疗中的机制,应用和挑战.
- 突出最近的进展和BsAb发展的未来方向,特别是在固体瘤中.
主要方法:
- 对T细胞激活双特异性抗体的现有文献的综述.
- 对临床试验数据和临床前研究结果的分析.
- 讨论目标选择,耐药性机制和毒性概况.
主要成果:
- BsAbs在白血病,淋巴瘤和骨髓瘤等血液癌症中表现出显著的活性.
- 在针对gp100/ HLA- A2: 01的不可切除或转移性乳膜黑色素瘤中观察到有希望的结果.
- 细胞因子释放综合征是一种主要的毒性,源于T细胞激活.
结论:
- BsAbs是一种有效的治疗方法, 在血液癌症中已被证明有效.
- 克服目标特异性的挑战对于扩大BsAb在固体瘤中的疗效至关重要.
- 目前正在进行的新形式和组合策略研究旨在提高治疗结果.
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