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赫克萨Body-CD38的临床前抗瘤活性,这是下一代CD38抗体,具有卓越的补充依赖细胞毒性活性

Ida H Hiemstra¹, Kim C M Santegoets¹, Maarten L Janmaat¹

¹Genmab B.V., Utrecht, the Netherlands.

|June 28, 2023

概括

HexaBody-CD38是一种新型抗体,通过增强补充依赖性细胞毒性 (CDC) 和对表达CD38的癌症的其他免疫反应,显示出强大的抗癌活性. 临床前研究支持其在多发性骨髓瘤患者的临床评估.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

赫克萨Body-CD38 (GEN3014) 是一种针对CD38.8的工程IgG1抗体.
它利用E430G突变促进抗体六体化,增强C1q结合和补充依赖性细胞毒性 (CDC).

研究的目的:

描述Hexabody-CD38的结合和疗效.
在临床前模型中评估其抗瘤活性和作用机制.

主要方法:

同结晶研究以确定结合界面.
流细胞计测定用于CDC,ADCC,ADCP,细胞和亡.
对CD38.8的酶活性测定.
在体内研究使用患者衍生的异种移植小鼠模型.

主要成果:

HexaBody-CD38结合一个独特的CD38表位,诱导多发性髓瘤,AML和B-NHL细胞系中的强有力的CDC.
它在体内表现出抗瘤活性,并且在低CD38表达细胞中与达拉图姆相比增强了CDC,而没有溶解健康白细胞.
该抗体还诱导了ADCC,ADCP,细胞,亡,并抑制了CD38环酶活性.

结论:

HexaBody-CD38通过多种免疫机制表现出强大的临床前抗癌活性.
它抑制CD38酶活性的能力可能减轻免疫抑制.
这些发现导致启动了一项临床试验,以评估多发性骨髓瘤患者的安全性.

关键词:

抗体是对抗体的一种.CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 CD38 补充依赖的细胞毒性达拉图姆巴姆巴姆血液学新生体的新生体.多发性骨髓瘤是一种多发性骨髓瘤.

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