Imaging mass spectrometry for the precise design of antibody-drug conjugates.
Imaging mass spectrometry for the precise design of antibody-drug conjugates.
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DOI：
10.1038/srep24954
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发表时间：
2016-04-21
影响因子：
4.6
通讯作者：
Matsumura Y
中科院分区：
文献类型：
--
作者：
Fujiwara Y;Furuta M;Manabe S;Koga Y;Yasunaga M;Matsumura Y
抗体-药物结合物(ADC)是一类能够将细胞毒药物输送到靶向肿瘤细胞的免疫治疗剂。由于多种肿瘤和肿瘤血管内皮细胞强烈表达抗人组织因子(Tf)，我们制备了由Tf特异性的单抗(MAb)与抗癌剂(ACA)单甲基金黄色E(MMAE)通过Valine-Cit(Val-Cit)连接物(人Tf ADC)连接而成的ADC。由于ADC具有复杂的结构，因此很难提前确定最有效的药物设计。评估ADC的最好方法是检查它们在肿瘤组织中释放和分布ACA的选择性和效率。基质辅助激光解吸电离成像质谱仪(MALDI-IMS)可用于直接检测天然分子在肿瘤组织中的分布。在这里，MALDI-IMS能够识别从ADC释放的MMAE在肿瘤内的分布。总之，MALDI-IMS是评估ADC和促进ADC设计优化的有用工具。
Antibody-drug conjugates (ADCs) are a class of immunotherapeutic agents that enable the delivery of cytotoxic drugs to target malignant cells. Because various cancers and tumour vascular endothelia strongly express anti-human tissue factor (TF), we prepared ADCs consisting of a TF-specific monoclonal antibody (mAb) linked to the anticancer agent (ACA) monomethyl auristatin E (MMAE) via a valine-citrulline (Val-Cit) linker (human TF ADC). Identifying the most efficient drug design in advance is difficult because ADCs have complicated structures. The best method of assessing ADCs is to examine their selectivity and efficiency in releasing and distributing the ACA within tumour tissue. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can be used to directly detect the distributions of native molecules within tumour tissues. Here, MALDI-IMS enabled the identification of the intratumour distribution of MMAE released from the ADC. In conclusion, MALDI-IMS is a useful tool to assess ADCs and facilitate the optimization of ADC design.