Pertuzumab (also known as 2C4; trade name Perjeta) is a humanized monoclonal antibody that acts as a HER2 dimerization inhibitor for the treatment of metastatic HER2-positive breast cancer. Pertuzumab is used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in early HER2-positive breast cancer
| In vitro | Trastuzumab and Pertuzumab are highly synergistic inhibitors of BT474 breast cancer cell survival. The combination of trastuzumab and Pertuzumab mediates a loss of up to 60% of cells at doses in which individual drugs do not alter cell survival. The combination of trastuzumab and Pertuzumab reduces the percentage of proliferating (S-phase) cells by more than 2-fold. A combination of trastuzumab and Pertuzumab inhibits cell proliferation and survival to a greater degree than does either agent alone. |
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| In Vivo | In Calu-3 NSCLC xenografts, monotherapy with pertuzumab or trastuzumab is able to significantly inhibit tumor growth, with treatment-to-control ratios (TCR) of 0.23 and 0.27, respectively. The combination of trastuzumab and pertuzumab produces a dramatically enhanced antitumor activity compared with single-agent treatments (TCR 0.05, resulting in tumor regression and, in 3 of 10 animals, complete tumor remission). Treatment of KPL-4 breast cancer xenografts with either trastuzumab or pertuzumab inhibits tumor growth with TCRs of 0.67 and 0.65, respectively. Pertuzumab maintains antitumor activity after progression on trastuzumab. |
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| Protocol | Cell Assay: BT474 cells are seeded at 5×104 cells/well in 12-well dishes. After 24 h, cells are treated in triplicate with 2-fold serial dilutions of trastuzumab, Pertuzumab, or both drugs simultaneously at a fixed 1:1 ratio at low doses ranging from 0.9 ng/mL to 10 ng/mL. After 5 days, cells are trypsinized and counted by trypan blue exclusion. Growth inhibition is calculated as the percentage of viable cells compared with untreated cultures.
Animal Studies: Calu-3 or KPL-4 tumors (100 mm3) are treated with trastuzumab (30 mg/kg loading dose, then 15 mg/kg weekly), Pertuzumab (30 mg/kg loading dose, then 15 mg/kg weekly), or both, administered i.p. for the duration of the study. Tumor volumes and body weights are measured twice weekly. For the acute study, advanced Calu-3 tumors of 400 mm3 are treated once with trastuzumab and/or Pertuzumab at a dose of 30 mg/kg. Samples are harvested 7 d later for immunohistochemistry (IHC) and Western blot analysis. |
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| References | Cancer Res. 2004 Apr 1;64(7):2343-6.; Cancer Res. 2009 Dec 15;69(24):9330-6.
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