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针对领导序列cathepsin G衍生的免疫疗法

Chunhua Shi¹, Ze Tian¹, Jun Yan¹

¹Oncology Research for Biologics and Immunotherapy Translation (ORBIT), University of Texas MD Anderson Cancer Center, Houston, TX, USA.

|February 12, 2025

概括

一种针对急性髓性白血病 (AML) 细胞的特定 (CG1) 的新型双特异性抗体显示出强大的抗白血病活性. 这种免疫疗法有效地杀死AML细胞,同时保存正常的骨髓,支持临床发展.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物化学生化学

背景情况:

骨髓性青色素颗粒含有细胞内白血病抗原,包括Cathepsin G (CG).
在急性髓性白血病 (AML) 爆发中,相对于正常的髓性原始体,cathepsin G的表达更高.
该HLA-A*0201 (HLA-A2) 分子首选呈现领导序列 (LS) 衍生的,如CG1 (FLLPTGAEA).

研究的目的:

设计和评估一种新型双特异性抗体 (CG1/A2xCD3),针对AML免疫治疗的CG1/HLA-A2复合体.
评估CG1/A2xCD3在向急性髓性白血病的临床前疗效和安全性.

主要方法:

设计一种针对CG1/HLA-A2复合体的T细胞参与剂双特异性抗体 (CG1/A2xCD3).
对CG1/HLA-A2单体,CD3-Fc融合蛋白和AML/T细胞的结合 afinity 的评估.
在体外和体内杀死HLA-A2+原发性AML和细胞系的评估.
监测T细胞激活,细胞因子分泌和对正常骨髓的活性.

主要成果:

CG1/A2xCD3对目标复合体和细胞具有很高的结合亲和力.
该抗体在体外和体内都诱导了主要AML和细胞系的强有力的杀死.
观察到依赖瘤和抗体的T细胞激活和细胞因子分泌.
CG1/A2xCD3对正常的骨髓细胞没有活性.

结论:

针对像CG1这样的领导序列衍生的,代表了AML免疫治疗的可行策略.
新型双特异性抗体CG1/A2xCD3显示出前临床有效性和安全性的前景.
这些发现支持CG1/A2xCD3的持续临床开发,用于治疗急性髓性白血病.

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