人源化单克隆抗体抑制碳酸酐酶 12 的酶活性可导致肿瘤生长减少。
Humanized Monoclonal Antibody Blocking Carbonic Anhydrase 12 Enzymatic Activity Leads to Reduced Tumor Growth .
机构信息
Cancer Immunology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
School of Pharmaceutical Sciences, Faculty of Sciences, University of Geneva, Geneva, Switzerland.
出版信息
Anticancer Res. 2019 Aug;39(8):4117-4128. doi: 10.21873/anticanres.13570.
BACKGROUND/AIM: Carbonic anhydrase 12 (CA12) is a membrane-associated enzyme that is highly expressed on many human cancers. It is a poor prognostic marker and hence an attractive target for cancer therapy. This study aimed to develop a humanized CA12-antibody with anti-cancer activity.
MATERIALS AND METHODS
Antibody libraries were constructed and screened by the Retrocyte display®. Antibody binding and blocking properties were determined by ELISA, flow cytometry and enzymatic activity assays. Spheroid viability was determined by Cell-Titer-Fluor assay.
RESULTS
We developed a novel humanized CA12-specific antibody, 4AG4, which recognized CA12 as an antigen and blocked CA12 enzymatic activity. Our humanized CA12-antibody significantly inhibited spheroid growth of lung adenocarcinoma A549-cells in vitro by blocking CA12 enzymatic activity. Similar anti-tumor effects were recapitulated with CA12-gene knockout of A549-cells.
CONCLUSION
Our newly identified humanized CA12-antibody with anti-cancer activity, represents a new tool for the treatment of CA12-positive tumors.
背景/目的：碳酸酐酶 12（CA12）是一种膜相关酶，在许多人类癌症中高度表达。它是一种预后不良的标志物，因此是癌症治疗的一个有吸引力的靶点。本研究旨在开发具有抗癌活性的人源化 CA12 抗体。
材料和方法
通过 Retrocyte display®构建和筛选抗体文库。通过 ELISA、流式细胞术和酶活性测定来确定抗体的结合和阻断特性。通过 Cell-Titer-Fluor 测定法来确定球体的活力。
结果
我们开发了一种新型的人源化 CA12 特异性抗体 4AG4，它将 CA12 识别为抗原并阻断 CA12 的酶活性。我们的人源化 CA12 抗体通过阻断 CA12 酶活性，显著抑制了体外肺腺癌细胞 A549 球体的生长。在 A549 细胞中敲除 CA12 基因也重现了类似的抗肿瘤作用。
结论
我们新发现的具有抗癌活性的人源化 CA12 抗体，为治疗 CA12 阳性肿瘤提供了一种新的工具。
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