Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Immunotherapy. 2014;6(1):43-9. doi: 10.2217/imt.13.156.
HER2 proto-oncogene is critical in the biology of breast cancer and an important therapeutic target of monoclonal antibodies (mAbs). We have recently established a panel of anti-HER2 mAbs recognizing different epitopes within the extracellular domain of HER2.
MATERIALS & METHODS: In the present study the antiproliferative effect of these mAbs was investigated on HER2-overexpressing human breast cancer cell line BT474, using radioactive thymidine incorporation assay.
Our results demonstrated that while two of the mAbs (1T0 and 2A8) inhibited cell proliferation dose dependently, similar to trastuzumab, six mAbs (1F2, 1B5, 1H9, 4C7, 1H6 and 2A9) augmented cell proliferation. Treatment of BT474 cells with different combinations of two mAbs induced either synergistic inhibitory or stimulatory effects.
Our findings indicate that combination of some stimulatory mAbs could completely abolish the inhibitory effect of other mAbs against HER2. Employment of some combinations of mAbs with significant synergistic inhibitory function may improve the therapeutic efficacy of HER2-specific mAbs.
HER2 原癌基因在乳腺癌的生物学中起着关键作用，是单克隆抗体（mAbs）的重要治疗靶点。我们最近建立了一组抗 HER2 mAbs，可识别 HER2 细胞外结构域内的不同表位。
在本研究中，我们使用放射性胸腺嘧啶掺入测定法，研究了这些 mAbs 在过表达 HER2 的人乳腺癌细胞系 BT474 上的抗增殖作用。
我们的结果表明，虽然两种 mAbs（1T0 和 2A8）与曲妥珠单抗类似，呈剂量依赖性抑制细胞增殖，但另外六种 mAbs（1F2、1B5、1H9、4C7、1H6 和 2A9）则增强了细胞增殖。用两种 mAbs 的不同组合处理 BT474 细胞，可诱导协同抑制或刺激作用。
我们的研究结果表明，某些刺激型 mAbs 的组合可能会完全消除其他针对 HER2 的 mAbs 的抑制作用。使用具有显著协同抑制功能的某些 mAbs 组合可能会提高 HER2 特异性 mAbs 的治疗效果。
