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. 2021 Jun 18;12:3790. doi: 10.1038/s41467-021-23948-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — a Lysed xenograft tumors taken from the final sacrifice, analyzed by immunoblotting, revealed severe reduction of total HER2 (tHER2), pHER2, pHER3, and pERK for 441-treated animals. mAb treatment-induced hyperphosphorylation of HER3 and ERK compared to PBS samples. mAb combinations revealed mixed responses. b Flow cytometric analysis of surface HER2 of cell lines established from mouse tumor material showed a loss of around 20% median intensity for 441-treated tumors. In contrast, HER2 levels stayed the same or were even augmented for TZB plus hA21G-treated animals. TZB and PZB induced a slight loss. c Cell lines derived from treated mouse tumors were challenged with indicated agents in a viability assay (n = 3 biological replicates, mean plus error bar SD, connected points, no fit). 441 was still able to reduce the proliferation the most among all studied agents. Tumors derived from 441-treated animals were also responsive to treatments; however, one TZB + hA21G-derived cell line had become practically resistant to treatments (thick dark-yellow line). Source data are available in the Source Data file.