Rapid generation of in vitro multicellular spheroids for the study of monoclonal antibody therapy.
Rapid generation of in vitro multicellular spheroids for the study of monoclonal antibody therapy.
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快速生成体外多细胞球体，用于研究单克隆抗体治疗。
DOI：
10.7150/jca.2.507
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发表时间：
2011
影响因子：
3.9
通讯作者：
Ho M
中科院分区：
文献类型：
--
作者：
Phung YT;Barbone D;Broaddus VC;Ho M
肿瘤微环境对抗体和免疫缀合物的渗透存在显著障碍，并且难以在体外研究。作为单层培养的细胞通常比体内生长的细胞表现出更少的治疗抗性。因此，重要的是开发一种替代的研究模型，更好地代表体内肿瘤。我们已经开发了一种产生多细胞球体的方案，这是一种简单且更相关的体内肿瘤模型，可以进一步研究微环境对药物渗透和肿瘤细胞杀伤的影响。该方案用于从建立的人癌细胞系和从患者分离的原代癌细胞中产生体外三维肿瘤球状体，而不使用任何细胞外组分。为了研究肿瘤靶向免疫偶联物在体外穿透这些肿瘤球体的能力，我们使用了靶向间皮素（一种在恶性间皮瘤中表达的表面蛋白）的免疫毒素。这种用于产生一致的、可再现的3D球状体的方法可以允许改进新型单克隆抗体和其他药剂的测试，以测试它们穿透实体瘤用于癌症治疗的能力。
Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellular spheroids, a simple and more relevant model of in vivo tumors that allows for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. The protocol is used to produce in vitro three-dimensional tumor spheroids from established human cancer cell lines and primary cancer cells isolated from patients without the use of any extracellular components. To study the ability of tumor-targeting immunoconjugates to penetrate these tumor spheroids in vitro, we have used an immunotoxin targeting mesothelin, a surface protein expressed in malignant mesotheliomas. This method for producing consistent, reproducible 3D spheroids may allow for improved testing of novel monoclonal antibodies and other agents for their ability to penetrate solid tumors for cancer therapy.
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影响因子：
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作者：
Ivascu, Andrea;Kubbies, Manfred
通讯作者：
Kubbies, Manfred
影响因子：
3
作者：
Torisawa, Yu-Suke;Mosadegh, Bobak;Takayama, Shuichi
通讯作者：
Takayama, Shuichi
DOI：
10.1039/c0an00609b
发表时间：
2011-02-07
期刊：
The Analyst
影响因子：
--
作者：
Tung YC;Hsiao AY;Allen SG;Torisawa YS;Ho M;Takayama S
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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影响因子：
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作者：
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通讯作者：
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