帕妥珠单抗（抗人 HER2，人源化抗体）是指定为 HER 二聚化抑制剂的新型药物中的第一个，是一种人源化 IgG1 单克隆抗体 (mAb)，可空间结合 erbB2 受体的结构域 II。
Pertuzumab (Anti-Human HER2, Humanized Antibody), the first of a new class of agents designated as HER dimerisation inhibitors, is a humanised IgG1 monoclonal antibody (mAb) that sterically binds domain II of the erbB2 receptor [1].
Pertuzumab may mostly act to inhibit the classical signaling pathways stimulated by active HER2, including receptor dimerization, receptor phosphorylation and the activation of signaling proteins downstream from HER receptors, including Erk and Akt [2].
Pertuzumab was approved by the FDA in 2012 to be used in combination with trastuzumab and docetaxel for treating metastatic breast cancer patients [2]. In humans, pooled analysis from one phase IA and two phase II studies in advanced disease evaluated pertuzumab pharmacokinetic parameters demonstrated minor interpatient variability in clearance and volume distribution when pertuzumab was administered with a fixed dose or based on weight (mg/kg). This supports the use of fixed dosing of pertuzumab, with an initial loading dose (840 mg) followed by a fixed dose of 420 mg every 3 weeks [3].
参考文献:
[1]. K El-Sahwi, S Bellone, E Cocco, et al. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. Br J Cancer, 102 (2010), pp. 134-143
[2]. Nami B, Maadi H, Wang Z. Mechanisms underlying the action and synergism of trastuzumab and pertuzumab in targeting HER2-positive breast cancer. Cancers (Basel) 2018;10
[3]. Capelan, M. et al. Pertuzumab: new hope for patients with HER2-positive breast cancer. Ann. Oncol. 24, 273-282 (2013).
帕妥珠单抗（抗人 HER2，人源化抗体）是指定为 HER 二聚化抑制剂的新型药物中的第一种，是一种人源化 IgG1 单克隆抗体 (mAb)，可空间结合 erbB2 受体的结构域 II [ 1].
帕妥珠单抗可能主要抑制由活性 HER2 刺激的经典信号通路，包括受体二聚化、受体磷酸化和 HER 受体下游信号蛋白的激活，包括 Erk 和 Akt [2]。
帕妥珠单抗于 2012 年获得 FDA 批准与曲妥珠单抗和多西他赛联合用于治疗转移性乳腺癌患者[2]。在人类中，一项 IA 期和两项 II 期晚期疾病研究的汇总分析评估了帕妥珠单抗药代动力学参数，表明当帕妥珠单抗以固定剂量或基于体重 (mg/kg) 给药时，清除率和体积分布的患者间差异很小。这支持使用固定剂量的帕妥珠单抗，初始负荷剂量 (840 mg) 随后每 3 周固定剂量 420 mg [3]。
| Cell experiment [1]: | |
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Cell lines |
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Preparation Method |
Primary USPC cells were seeded in a 96-well plate at a density of 2000-5000 cells per well in RPMI 1640 medium with 10% foetal bovine serum. After 24 h, pertuzumab, trastuzumab, and a 1 : 1 combination of both antibodies were added at a final concentration of 20 μg ml-1. The final volume of medium per well was set at 100 μl for 48-72 h |
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Reaction Conditions |
20 μg ml-1 for 48-72 hours |
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Applications |
Cell proliferation was significantly inhibited in the presence of pertuzumab, trastuzumab, and the combination of the two mAbs in all USPC cell lines tested, with the percentage of inhibition varying from 4 to 59% (pertuzumab), 3 to 48% (trastuzumab), and 7 to 63% (mAbs combination) in multiple experiments. |
| Animal experiment [2]: | |
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Animal models |
Male CD-1 mice |
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Preparation Method |
Pertuzumab (26.7 mg/mL) and vehicle (10 mM L-histidine at pH 6.0, 240 mM sucrose, 0.02% polysorbate 20) were stored at 2-8℃. |
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Dosage form |
3, 30, or 90 mg/kg, intravenous (IV) bolus. |
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Applications |
The distribution phase of pertuzumab was |
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参考文献: [1]: K El-Sahwi, S Bellone, E Cocco, et al. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. Br J Cancer, 102 (2010), pp. 134-143 |
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