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 .
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Background:

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).

Protocol:

Cell experiment [1]:
Cell lines
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
Reaction Conditions	20 µg ml-1 for 48-72 hours
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]:
Animal models	Male CD-1 mice
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℃.
Dosage form	3, 30, or 90 mg/kg, intravenous (IV) bolus.
Applications	The distribution phase of pertuzumab was<1 day, the terminal elimination half-life was approximately 10 days, and the volume of distribution was 27-58 mL/kg.
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]: C.W. Adams, D.E. Allison, K. Flagella, L. Presta, J. Clarke, N. Dybdal, et al. Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab Cancer Immunol Immunother, 55 (2006), pp. 717-727