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HPN328是一种三特性的T细胞激活蛋白构造,向DLL3-表达固体瘤

Mary E Molloy¹, Wade H Aaron¹, Manasi Barath¹

¹Harpoon Therapeutics, South San Francisco, California.

Molecular cancer therapeutics

|April 26, 2024

概括

HPN328是一种新的双特异性T细胞参与者,有效地准小细胞肺癌中的Delta样联体3 (DLL3). 临床前研究显示强烈的抗瘤活性和良好的安全性,支持正在进行的临床试验.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
药理学药理学是指药理学的学科.

背景情况:

小细胞肺癌 (SCLC) 具有侵略性,治疗选择有限.
甲状腺样联体3 (DLL3) 是一个有前途的标,在70%以上的SCLC中存在.
需要新的治疗策略来改善患者的预后.

研究的目的:

评估HPN328的临床前疗效和安全性,这是一种DLL3向的三种特异性T细胞激活结构 (TriTAC).
评估HPN328的作用机制,包括T细胞激活和抗瘤反应.
为了确定HPN328.8的药理动力学特征和耐受性.

主要方法:

在体外测定使用DLL3表达的SCLC细胞系.
在动物异种移植和免疫能力模型中的体内研究.
对非人类灵长类动物进行药理动力学和安全性评估的研究.

主要成果:

在实验室中,HPN328证明了强效的,剂量依赖的SCLC细胞杀死和T细胞激活.
已确定的瘤在HPN328治疗后显示出显著的抗瘤活性和T细胞招募.
在重新挑战模型中观察到长期抗瘤免疫力.
在Cynomolgus子中,HPN328被很好地容忍,可预测的药理动力学支持不频繁的剂量.

结论:

HPN328具有强大的临床前疗效和良好的安全性.
药物的机制涉及强大的T细胞介导的瘤细胞杀死.
HPN328代表了DLL3表达性恶性瘤的有前途的治疗候选者,目前正在进行1/2期试验.

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