Selection and analysis of anti-cancer antibodies for cancer therapy obtained from antibody phage library
Selection and analysis of anti-cancer antibodies for cancer therapy obtained from antibody phage library
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DOI：
10.1111/j.1349-7006.2010.01739.x
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发表时间：
2011-01-01
期刊：
影响因子：
5.7
通讯作者：
Kurosawa, Yoshikazu
中科院分区：
文献类型：
--
作者：
Kurosawa, Gene;Sumitomo, Mariko;Kurosawa, Yoshikazu
寻找用于可治愈的癌症免疫治疗的有效抗体（Ab）一直是许多研究小组的追求，以便找到存在于癌细胞表面的有效靶点。到目前为止，还没有结论性的答案来阐明搜索。因此，本研究旨在弥合癌症治疗的差距。对属于11种实体癌的49种细胞系进行筛选。此后还对约4200种单克隆抗体（mAb）进行了分离和表征。在这些mAb中，488个克隆结合29种肿瘤相关抗原（TAA），进行免疫组织化学（IHC）分析。在临床检查之前进行靶抗原（Ag）和用于癌症治疗的潜在抗体的选择。为了找到针对实体癌的治疗性Ab的可预测的有效靶标，使用从患者切除的新鲜癌症标本通过IHC分析广泛地检查了癌症和正常细胞表面上的Ag表达。本研究报告了各种染色模式的趋势和Ab的分布。虽然所有的TAA似乎都参与了肿瘤的发生，但它们的表达并不局限于某些特定的肿瘤类型，而是随机分布在各种癌症中。抗表皮生长因子受体（EGFR）和抗人表皮生长因子受体2（HER 2）等抗体在正常细胞中的表达频率普遍较低。因此，本研究中488 mAb的鉴定和IHC分析的累积结果可能是进一步治疗性Ab的关键。预期显示癌症特异性表达的靶标对于治疗性Ab比其它Ab更好。此外，使用完整人IgG形式的Ab对癌细胞系生长的进一步研究显示出在特定情况下的有效性。（Cancer Sci 2011; 102：175-181）。
The search for effective antibodies (Ab) for curable cancer immunotherapy has been a quest of many research groups in order to find an effective target that exists on the cancer cell surface. So far there have been no conclusive answers to shed light on the search. This study therefore aimed to bridge the gap of cancer therapy. Screening against 49 kinds of cell lines belonging to 11 kinds of solids cancers was performed. Isolation and characterization for approximately 4200 monoclonal antibodies (mAb) was also performed thereafter. Of those mAb 488 clones that turned out to bind to 29 tumor-associated antigens (TAA) were subjected to immunohistochemical (IHC) analyses. Selection of target antigens (Ag) and a potential antibody for cancer therapy was conducted prior to clinical examinations. In order to find predictably effective targets for therapeutic Ab against solid cancers, expression of the Ag on the surface of cancer and normal cells was extensively examined by IHC analyses using fresh cancer specimens resected from patients. In this study, the tendencies of all staining patterns and distribution of the Ab are reported. While all of the TAA appeared to be involved in tumorigenesis, their expression was not restricted to some specific tumor types but rather randomly distributed among various cancers. Some kinds of Ab including anti-epidermal growth factor receptor (EGFR) and anti-human epidermal growth factor receptor 2 (HER2) indicated the frequency of expression in normal cells was generally low. We concluded that identification of 488 mAb and the accumulated results of IHC analyses in this study could be the key for further therapeutic Ab against cancers. The targets that showed cancer-specific expression are expected to be better for therapeutic Ab than the other Ab. Moreover, further investigation into the growth of cancer cell lines using full human IgG form of Ab shows available efficacy in specific cases. (Cancer Sci 2011; 102: 175-181).