摘要
自从1975年Kohler和Milstein发现单克隆抗体以来的四十年,现在已有十几种抗体被用在具有不同策略的癌症靶向治疗中。成功其中的抗体依赖于在癌细胞上表达的抗原的特异性。上皮细胞粘附分子(EpCAM)是一种嗜同性细胞粘附糖蛋白,是一种广为人知的肿瘤。抗原,在上皮性肿瘤、循环肿瘤细胞和肿瘤干细胞上表达。EpCAM信号通路与e的增殖、分化和粘附有关。上皮癌细胞。本文综述了EpCAM的结构、表达谱及其在癌细胞中的信号转导途径。此外,我们还重点研究了抗EPCA的结构、作用机制和成功。M抗体已用于不同的临床试验。根据文献,Edrecolomab在第三阶段的研究中显示出有限的疗效。全人单克隆抗体Adecatumab是表达EpCAM的转移性乳腺癌患者的剂量和靶点依赖性。嵌合抗体Catumaxomab已被批准用于治疗恶性腹水,但此单克隆抗体显示。d癌症患者胸膜内给药效果显著。抗EpCAM毒素结合抗体,Oportuzumab Monatox(ScFv抗体和假单胞菌外毒素A),CitatuzumabBogatox(含布加宁毒素的Fab片段)和单抗Tucotuzumab(与IL2结合的单克隆抗体)在不同的临床试验中取得了令人满意的结果。几乎,所有的蚂蚁异物具有良好的耐受性;然而,还需要更多的临床试验来批准用于治疗特定肿瘤的抗体。
关键词: 癌症,靶向治疗,EpCAM,单克隆抗体,糖蛋白,Catumaxomab。
Current Cancer Drug Targets
Title:Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update
Volume: 18 Issue: 9
关键词: 癌症,靶向治疗,EpCAM,单克隆抗体,糖蛋白,Catumaxomab。
摘要: Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.
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Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update, Current Cancer Drug Targets 2018; 18 (9) . https://dx.doi.org/10.2174/1568009618666180102102311
DOI https://dx.doi.org/10.2174/1568009618666180102102311 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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