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DR30318,一种新的三特异性T细胞参与者,用于克劳丁18.2阳性癌症免疫治疗

Zhe Ma^1,2, Zhenxing Zhou², Wenwen Duan²

¹Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China.

Cancer immunology, immunotherapy : CII

|March 30, 2024

概括

一种新的三特异性T细胞激活剂DR30318针对胃癌和胰腺癌的克劳丁18.2 (CLDN18.2). 这种疗法在临床前模型中显示出显著的瘤抑制和T细胞介导的细胞毒性.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
分子生物学分子生物学

背景情况:

克劳丁18.2 (CLDN18.2) 是固体瘤,特别是胃癌和胰腺癌的有前途标.
针对CLDN18.2的T细胞参与者提供了一种强有力的策略,以促进抗癌免疫反应.

研究的目的:

开发和评估一种针对胃和胰腺癌的CLDN18.2的新型三特异性T细胞吸引剂.
评估针对CLDN18.2的T细胞吸引剂的疗效和药理动力学特性.

主要方法:

开发一种三特异性抗体 (DR30318) 结合CLDN18.2,人类血清白蛋白 (HSA) 和CD3.
在体外评估结合亲和力,T细胞依赖细胞细胞毒性 (TDCC) 和细胞因子产生 (IL-6,IFN-γ).
在胃癌和胰腺癌异种移植模型中的体内评估,包括药理动力学分析和体重监测.

主要成果:

DR30318表现出对CLDN18.2,HSA和CD3的结合,并证明了体外TDCC活性.
药理动力学研究表明,动物的半衰期为22.2-28.6小时,猿的半衰期为41.8小时.
在胃癌和胰腺癌异种移植模型中观察到显著的瘤抑制,对体重没有不良影响,伴随着诱导的细胞因子产生.

结论:

三特异性T细胞参与者DR30318显示出强大的抗瘤活性,可对抗CLDN18.2-表达的胃癌和胰腺癌.
DR30318有效地重定向T细胞以消除癌细胞,支持其作为新型免疫疗法的潜力.
临床前数据表明DR30318是进一步临床开发固体瘤治疗的有希望的候选人.

关键词:

克劳迪因 18.2 克劳迪因细胞因子 (cytokines) 是一种细胞因子.胃癌是什么?胃癌是什么?胰腺癌是一种胰腺癌.一个T细胞参与者.这是TDCC的TDCC.

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