Possible Therapeutic Utility of anti-Cell Adhesion Molecule 1 Antibodies for Malignant Pleural Mesothelioma.
Possible Therapeutic Utility of anti-Cell Adhesion Molecule 1 Antibodies for Malignant Pleural Mesothelioma.
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DOI：
10.3389/fcell.2022.945007
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
恶性胸膜间皮瘤（MPM）是一种高度侵袭性的恶性肿瘤，有效的治疗药物有限。因此，需要建立新的治疗方法。相当比例的MPM显示表达细胞粘附分子1（CADM 1），并使用CADM 1结合到胸膜间皮表面并在其上增殖，这表明CADM 1是可能的治疗靶点。在此，检查抗CADM 1胞外域鸡单克隆抗体3E 1和9D 2的可能治疗效用。CADM 1的全长形式在12个人MPM细胞系中的8个中表达。在存在中和抗体9D 2的情况下，将MPM细胞系培养在间皮细胞MeT-5A细胞的汇合单层上。9D 2抑制CADM 1阳性MPM细胞的细胞生长，伴随CADM 1分子在MPM细胞膜上的损失和聚集，但不抑制CADM 1阴性MPM细胞。缺乏中和作用的3E 1的共添加增强了9D 2的生长抑制作用。将两种抗体作为药物递送载体进行测试。将3E 1转化为人源化抗体（h3 E1）并与微管蛋白聚合抑制剂单甲基澳瑞他汀E（MMAE）缀合。当将所得h3 E1-MMAE抗体-药物缀合物（ADC）加入CADM 1阳性MPM细胞的标准培养物中时，其以剂量依赖性方式抑制细胞生长。9D 2的共添加增强了h3 E1-MMAE ADC的生长抑制作用。抗CADM 1胞外域抗体被认为是治疗MPM的抗体药物和药物载体。
Malignant pleural mesothelioma (MPM) is a highly aggressive malignant tumor, and the effective therapeutic drugs are limited. Thus, the establishment of novel therapeutic method is desired. Considerable proportion of MPMs are shown to express cell adhesion molecule 1 (CADM1), and to use CADM1 to bind to and proliferate on the pleural mesothelial surface, suggesting that CADM1 is a possible therapeutic target. Here, anti-CADM1 ectodomain chicken monoclonal antibodies, 3E1 and 9D2, were examined for their possible therapeutic utility. The full-length form of CADM1 was expressed in eight out of twelve human MPM cell lines. MPM cell lines were cultured on a confluent monolayer of mesothelial MeT-5A cells in the presence of 9D2, the neutralizing antibody. 9D2 suppressed the cell growth of CADM1-positive MPM cells with the loss and aggregation of CADM1 molecules on the MPM cell membrane, but not of CADM1-negative MPM cells. Co-addition of 3E1, lacking the neutralizing action, enhanced the growth-suppressive effect of 9D2. The two antibodies were tested as drug delivery vectors. 3E1 was converted into a humanized antibody (h3E1) and conjugated with monomethyl auristatin E (MMAE), a tubulin polymerization inhibitor. When the resulting h3E1–MMAE antibody-drug conjugate (ADC) was added to the standard cultures of CADM1-positive MPM cells, it suppressed the cell growth in a dose-dependent manner. Co-addition of 9D2 enhanced the growth-suppressive effect of h3E1–MMAE ADC. Anti-CADM1 ectodomain antibodies were suggested to serve as both antibody drugs and drug vectors in the treatment of MPM.
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影响因子：
56.9
作者：
Biederer, T;Sara, Y;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
4.4
作者：
Furuno, T;Ito, A;Kitamura, Y
通讯作者：
Kitamura, Y
影响因子：
2.7
作者：
Hagiyama M;Takeuchi F;Sugano A;Yoneshige A;Inoue T;Wada A;Kajiyama H;Takaoka Y;Sasaki K;Ito A
通讯作者：
Ito A
影响因子：
20.3
作者：
Francisco, JA;Cerveny, CG;Wahl, AF
通讯作者：
Wahl, AF
影响因子：
5.7
作者：
Golfier, Sven;Kopitz, Charlotte;Ziegelbauer, Karl
通讯作者：
Ziegelbauer, Karl