Antibody-Drug Conjugate to Treat Meningiomas.
Antibody-Drug Conjugate to Treat Meningiomas.
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DOI：
10.3390/ph14050427
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发表时间：
2021-05-02
期刊：
影响因子：
--
通讯作者：
Liu XM
中科院分区：
文献类型：
--
作者：
Chen K;Si Y;Ou J;Guan JS;Kim S;Ernst P;Zhang Y;Zhou L;Han X;Liu XM
脑膜瘤是中枢神经系统的原发性肿瘤，具有较高的复发率。据报道，生长抑素受体2（SSTR 2）在大多数脑膜瘤中高表达，但目前尚无有效的靶向治疗被批准用于控制脑膜瘤。本研究旨在开发和评估抗SSTR 2抗体-药物偶联物（ADC）靶向和治疗脑膜瘤。使用细胞系和/或颅内异种移植小鼠模型评价了SSTR 2 ADC的脑膜瘤靶向、循环稳定性、毒性和抗肿瘤功效。流式细胞仪分析显示，抗SSTR 2单抗与脑膜瘤细胞系CH 157-MN的结合率>98%，而与正常蛛网膜AC 07细胞的结合率<5%。体内成像系统（IVIS）成像显示Cy5.5标记的ADC靶向脑膜瘤异种移植物并在其中蓄积，但不在正常器官中蓄积。药代动力学研究和组织学分析证实了稳定性和最小毒性。体外抗癌细胞毒性表明ADC的高效力，IC 50值<10 nM。体内抗肿瘤功效显示，剂量为8和16 mg/kg体重的抗SSTR 2 ADC有效抑制肿瘤生长。本研究表明，抗SSTR 2 ADC可以靶向脑膜瘤并减少肿瘤生长。
Meningiomas are primary tumors of the central nervous system with high recurrence. It has been reported that somatostatin receptor 2 (SSTR2) is highly expressed in most meningiomas, but there is no effective targeted therapy approved to control meningiomas. This study aimed to develop and evaluate an anti-SSTR2 antibody–drug conjugate (ADC) to target and treat meningiomas. The meningioma targeting, circulation stability, toxicity, and anti-tumor efficacy of SSTR2 ADC were evaluated using cell lines and/or an intracranial xenograft mouse model. The flow cytometry analysis showed that the anti-SSTR2 mAb had a high binding rate of >98% to meningioma CH157-MN cells but a low binding rate of <5% to the normal arachnoidal AC07 cells. The In Vivo Imaging System (IVIS) imaging demonstrated that the Cy5.5-labeled ADC targeted and accumulated in meningioma xenograft but not in normal organs. The pharmacokinetics study and histological analysis confirmed the stability and minimal toxicity. In vitro anti-cancer cytotoxicity indicated a high potency of ADC with an IC50 value of <10 nM. In vivo anti-tumor efficacy showed that the anti-SSTR2 ADC with doses of 8 and 16 mg/kg body weight effectively inhibited tumor growth. This study demonstrated that the anti-SSTR2 ADC can target meningioma and reduce the tumor growth.
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影响因子：
0.9
作者：
Gottardi M;Mosna F;de Angeli S;Papayannidis C;Candoni A;Clavio M;Tecchio C;Piccin A;dell'Orto MC;Benedetti F;Martinelli G;Gherlinzoni F
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11.5
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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