Human Anti-ERBB3 Recombinant Antibody (clone KTN3379) (CAT#: PABL-086)

Figure 1 HPV+ HNSCC models are sensitive to therapeutic blockade of HER3 with the anti-HER3 monoclonal antibody, KTN3379.

A, HPV− and HPV+ HNSCC cell lines were treated with 100 nmol/L KTN3379 for 72 hours before performing proliferation assays. Proliferation is plotted as a percentage of growth relative to vehicle-treated cells (n = 6 in three-five independent experiments). Data points are represented as mean ± SEM. Whole-cell lysates were harvested from three HPV− cell lines (PECAPJ49, TU138, and SCC1), and three HPV+ cell lines (SCC47, 93-VU-147T, and SCC90) over a time course of 72 hours of KTN3379 treatment (100 nmol/L) followed by immunoblotting for the indicated proteins. β-Actin was used as a loading control. B, HPV+ cell lines (SCC47 and SCC90) were grown as xenografts in athymic nude mice (n = 6 tumors per treatment group for SCC47, and n = 4 tumors per treatment group for SCC90). The HPV+ PDX-10 was implanted into the dorsal flanks of NOD/SCIDγ mice (n = 6 tumors per treatment group). All xenografts were treated with KTN3379 (10 mg/kg) or vehicle twice weekly for the indicated time period by IP injection.

Brand, T. M., Hartmann, S., Bhola, N. E., Peyser, N. D., Li, H., Zeng, Y.,... & LaVallee, T. M. (2017). Human papillomavirus regulates HER3 expression in head and neck cancer: implications for targeted HER3 therapy in HPV+ patients. Clinical Cancer Research, 23(12), 3072-3083.

Figure 2 KTN3379 inhibits HER3 signaling and tumor growth in HER2-amplified cancer cells.

A: BT474 cells were treated with the indicated doses of KTN3379 or control IgG for 4 hours and then processed for ELISA analysis of pHER3 as indicated in Materials and Methods. Control represents untreated cells. B: BT474 cells were treated with the indicated doses of KTN3379 or control IgG for 4 hours and then processed for ELISA analysis of pAKT. Control represents untreated cells.

Xiao, Z., Carrasco, R. A., Schifferli, K., Kinneer, K., Tammali, R., Chen, H.,... & Tsui, P. (2016). A potent HER3 monoclonal antibody that blocks both ligand-dependent and independent activities: differential impacts of PTEN-status on tumor response. Molecular cancer therapeutics, molcanther-0555.

Figure 3 KTN3379 disrupts HER2-HER3 dimerization in both ligand-dependent and independent models.

A: T47D cells were pre-treated with control IgG or KTN3379 and then treated with HRG to induce HER2/HER3 dimer formation as detailed in Materials and Methods. Cells were lysed HER3 immunoprecipitation was performed with anti-HER3 antibody that targets the cytoplasmic domain. The precipitates were run on Western Blots and probed for HER2 and HER3 proteins. The various lanes were cropped from the same Western Blot. B: BT474 cells were pre-treated with control IgG or KTN3379 and then treated with the cross-linker DTSSP to stabilize HER2-HER3 dimer prior to cell lysis as detailed in Materials and Methods. Cells were lysed and HER3 immunoprecipitation was performed with anti-HER3 antibody that targets the cytoplasmic domain. The precipitates were run on Western Blots and probed for HER2 and HER3 protein levels. The various lanes were cropped from the same Western Blot.

Xiao, Z., Carrasco, R. A., Schifferli, K., Kinneer, K., Tammali, R., Chen, H.,... & Tsui, P. (2016). A potent HER3 monoclonal antibody that blocks both ligand-dependent and independent activities: differential impacts of PTEN-status on tumor response. Molecular cancer therapeutics, molcanther-0555.

Figure 4 KTN3379 preferentially suppresses tumor growth in HRG-dependent models in vivo.

B, C: KTN3379 were tested in vivo for its anti-tumor effects in Lung adenocarcinoma model A549 (B) and Colorectal cancer model HT29 (D). Unless otherwise indicated, KTN3379 was dosed at 10 while control IgG was dosed at similar level or higher levels (30mg/kg). All mAbs treatment (twice per week) was started when tumor size reached ~250mm³.

Xiao, Z., Carrasco, R. A., Schifferli, K., Kinneer, K., Tammali, R., Chen, H.,... & Tsui, P. (2016). A potent HER3 monoclonal antibody that blocks both ligand-dependent and independent activities: differential impacts of PTEN-status on tumor response. Molecular cancer therapeutics, molcanther-0555.