用细胞毒性治疗抗体向MICA/B导致瘤控制
Mathieu Bléry1, Manel Mrabet-Kraiem1, Ariane Morel1
1Innate Pharma, Marseille, France.
Open research Europe
|August 30, 2023
概括
研究人员开发了针对MICA和MICB蛋白的MICAB1抗体-药物联合体 (ADC). 这些ADC在临床前模型中显示出对固体瘤的显著控制,突出显示MICA和MICB是癌症免疫治疗的有希望的标.
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:
- MICA和MICB是压力诱导的蛋白质,在固体瘤上表达,与细胞毒性淋巴细胞上的NKG2D受体结合.
- 它们的瘤特异性表达和免疫性使MICA和MICB成为癌症治疗的有吸引力的标.
- 在MICA和MICB中的高多态性需要交叉反应的治疗剂.
研究的目的:
- 开发针对MICA和MICB的新型治疗抗体.
- 评估抗体-药物合物 (ADC) 对于固体瘤治疗的疗效.
主要方法:
- 产生交叉反应的抗MICA和MICB单克隆抗体 (mAbs).
- 人类IgG1 Fc变异抗体的工程,MICAB1.1.
- 在体外评估抗体依赖细胞细胞毒性 (ADCC) 和细胞化 (ADCP).
- 使用固体瘤模型的体内疗效研究,包括患者衍生异种移植 (PDX) 和MICAgen转基因小鼠.
主要成果:
- 在MICAB1 mAb显示强大的体外ADCC和ADCP对MICA/B表达瘤细胞.
- 在各种固体瘤模型中,MICAB1-ADC证明了最佳的瘤控制.
- 在免疫能力强的小鼠中,在PDX和致癌原诱导的瘤中观察到有效的向.
结论:
- MICA和MICB被证实是基于抗体-药物结合物的癌症免疫治疗的有希望的标.
- MICAB1-ADC代表了表达MICA/B.的固体瘤的潜在治疗策略.
- 针对MICA/B的ADC的进一步开发需要进行调查.
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