针对LGR5的新型免疫疗法可针对多种癌症类型
Hung-Chang Chen1,2, Nico Mueller1, Katherine Stott3
1University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
EMBO molecular medicine
|August 21, 2024
概括
一种针对富含白的重复含有G蛋白结合受体5 (LGR5) 的新型抗体显示出有前途. 这种抗体α-LGR5有效地向各种癌症,并作为开发强效免疫疗法的基础.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
背景情况:
- 富含白的重复含有G蛋白结合受体5 (LGR5) 在几个侵袭性癌症中过度表达,包括结直肠癌 (CRC),肝细胞癌 (HCC) 和B前急性淋巴细胞白血病 (B-ALL前).
- 向LGR5为这些恶性瘤提供了潜在的治疗策略.
研究的目的:
- 开发和验证一种针对人类LGR5 (α-LGR5) 细胞外域的特定抗体.
- 评估α-LGR5在各种形式的治疗潜力,包括抗体-药物合物 (ADC),双特异性T细胞参与者 (BiTEs) 和仿真抗原受体 (CAR) T细胞,以准LGR5表达性癌症.
主要方法:
- 开发和验证针对人类LGR5.5的特定抗体 (α-LGR5).
- 基于α-LGR5的免疫治疗方式的产生:抗体-药物联 (α-LGR5-ADC),双特异性T细胞参与者 (α-LGR5-BiTE) 和仿制抗原受体 (α-LGR5-CAR) T细胞.
- 在实验室和体内使用癌细胞系和人类B-ALL前的小鼠模型的实验室和体内疗效研究.
主要成果:
- α-LGR5在90%以上的CRC,HCC和B-ALL前瘤细胞中检测到LGR5过度表达.
- 在B-ALL前的小鼠模型中,α-LGR5-ADC在体外和体内表现出强大的抗瘤疗效,显著降低了瘤负担.
- 在体内,α-LGR5-BiTE和α-LGR5-CAR T细胞也显示出特定的癌细胞杀死和减少瘤负担.
结论:
- α-LGR5是一种多功能抗体,可以作为研究工具,生物标志物和开发新型免疫疗法的基本组成部分.
- 开发的基于α-LGR5的疗法为针对广泛的LGR5表达性癌症提供了一个有前途的组合.
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