用癌症特异的单克隆抗体向固体癌症,以表达异常O-糖化蛋白的表面
Mikkel K M Aasted1, Aaron C Groen2, John T Keane3
1Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
Molecular cancer therapeutics
|July 14, 2023
概括
研究人员开发了一种新型抗体,针对一种独特的癌细胞标记物CD44v6. 这种抗体在嵌合式抗原受体 (CAR) T 细胞中使用时,显示出选择性固体瘤免疫疗法的前景,并提高了安全性.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 目前针对固体瘤的免疫疗法受到癌症选择性抗体缺乏的限制,因为许多标也存在于健康组织中.
- 在固体瘤中异常的糖化形成了与瘤相关的独特碳水化合物抗原,为癌症特定向提供了潜在的潜力.
- 针对这些异常的葡萄糖表位是开发强效和选择性免疫疗法的有希望的策略.
研究的目的:
- 为了确定针对癌症的特定葡萄糖表位,用于向免疫疗法.
- 开发一种新型单克隆抗体 (mAb),准这种表位.
- 在固体瘤模型中评估基于mAb的仿真抗原受体 (CAR) T细胞的疗效和安全性.
主要方法:
- 利用O-glycoproteomics识别CD44v6中的一个独特的糖表位,一种与癌症相关的异型.
- 开发了一种癌症特异的mAb (4C8),使用糖免疫策略.
- 评估了4C8结合,通过免疫组织化学 (IHC) 的癌症特异性以及4C8CAR T细胞的体外/体内疗效.
主要成果:
- 鉴定并准了一种Tn-glycosylated CD44v6表位,具有癌症特异的mAb 4C8,表现出低纳米分子亲和力.
- 通过IHC在各种健康和癌症组织中证明了4C8的高癌症特异性.
- 4C8 CAR T 细胞表现出特定的细胞毒性,显著的瘤回归,以及体内生存率的增加,在混合癌症模型中选择性杀死.
结论:
- 用4C8 mAb准CD44v6糖表位,为免疫疗法提供一种高度选择性癌症治疗方法.
- 4C8 CAR T 细胞表现出强大的抗瘤活性和有利的安全性,不影响健康组织.
- 这一策略具有显著的潜力,可以通过向免疫疗法推进固体瘤的治疗.
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