Clin Cancer Res:抗ICAM1抗体-药物偶联物用于多发性骨髓瘤的潜在活性

2020-09-19 QQY MedSci原创

新疗法已经改变了多发性骨髓瘤(MM)患者的前景,但是对于难治性或采用目前获批药物治疗后复发的患者需要开发新的药物。随着对达雷木单抗和新出现的抗BCMA方法的耐药性的出现,我们需要除了CD38和BCMA

新疗法已经改变了多发性骨髓瘤(MM)患者的前景,但是对于难治性或采用目前获批药物治疗后复发的患者需要开发新的药物。随着对达雷木单抗和新出现的抗BCMA方法的耐药性的出现,我们需要除了CD38和BCMA以外的新靶点以开发新的免疫疗法。

ICAM1是骨髓瘤的一个潜在靶点。裸抗ICAM1抗体在骨髓瘤临床前模型中表现活跃,而且安全性好,但临床疗效有限。在近日发表了《Clinical Cancer Research》上的“Potent activity of an anti-ICAM1 antibody-drug conjugate against multiple myeloma”一文中,研究人员尝试通过抗ICAM1抗体-药物偶联物来改善抗ICAM1抗体对多发性骨髓瘤的靶向性。

研究人员将抗ICAM1人单克隆抗体与瑞奥西汀衍生物相偶联,并在多种多发性骨髓瘤细胞系、原位移植模型和患者样本中进行检测。此外,还通过定量流式细胞术检测了从确诊到达雷木单抗难治性疾病患者的ICAM1表达水平。

抗ICAM1抗体-药物偶联物在体内外均表现出了较强的抗骨髓瘤细胞毒性。此外,研究人员发现,ICAM1在骨髓瘤细胞中高表达,而且骨髓微环境因子的存在可进一步强化其表达。在原发样本中,与正常细胞相比,ICAM1在多发性骨髓瘤细胞中有差异性过表达,包括CD38降低的达雷木单抗难治性患者。而且,ICAM1-ADC对多发性骨髓瘤原始样本表现出了选择性的毒性。

根据上述研究结果,Sherbenou等人建议,应进一步在复发或难治性多发性骨髓瘤患者中评估抗ICAM1抗体-药物偶联物的毒性、安全性及临床疗效。

原始出处:

Daniel W Sherbenou, et al. Potent activity of an anti-ICAM1 antibody-drug conjugate against multiple myeloma. Clin Cancer Res September 18 2020 DOI:10.1158/1078-0432.CCR-20-0400

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    2020-10-18 whmdzju
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    2021-01-26 jml2009
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    2020-09-20 ms4000001836463517

    好文章

    0

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    2020-09-19 Nebula-Qin

    优秀

    0

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