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用于通过向美索他林来治疗固体瘤的T细胞重定向抗体

Jun-Jun Liu¹, Zhi-di Pan², Ya-Li Yue¹

¹Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.

Acta pharmacologica Sinica

|June 10, 2024

概括

一种新的T细胞参与双特异性抗体 (TCB),MSLN490,显示出强大的抗瘤活性,对抗表达美索林的癌症. 它仍然有效地对抗可溶性美索林,并与其他疗法协同作用,为固体瘤治疗提供了希望.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
生物技术是生物技术.

背景情况:

参与T细胞双特异性抗体 (TCBs) 正在成为癌症治疗中的重要治疗策略.
梅索林 (MSLN) 是一种在各种固体瘤中高度表达的标蛋白,使其成为癌症治疗的有前途标.

研究的目的:

开发和评估MSLN490,一种针对MSLN的新型TCB,其对固体瘤的有效性.
评估MSLN490在存在可溶性MSLN和与其他治疗剂结合时的活性.

主要方法:

使用CDR行走和菌体显示技术开发MSLN490,以增强对MSLN的亲和力.
具有IgG-[L]-scFv结构的双特异抗体 (BsAbs) 的组合.
在体外和与其他疗法 (如阿特佐利祖马布,TAA×CD28 BsAbs和帕克利塔塞尔) 结合使用的抗瘤活性的评估.

主要成果:

MSLN490对表达MSLN的瘤具有显著的抗瘤活性,EC50为0.16 pM.
抗体即使存在可溶性MSLN,也保持了有效性.
组合疗法,特别是帕克利塔塞尔,由于免疫细胞透的改善,显示出增强的抗瘤作用.

结论:

MSLN490对表达MSLN的固体瘤表现出强大而有弹性的抗瘤活性.
结合其他疗法,包括化疗,可以进一步提高它的疗效.
MSLN490代表了对各种固体瘤的有希望的治疗候选者,需要进一步的临床研究.

关键词:

美国MSLN49090号参与T细胞的双特异性抗体.梅索他林是其中一种.帕克利塔克塞尔 (paclitaxel) 是一种药物.固体瘤是一种固体瘤.

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