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. 2018 Mar 22;7(2):15. doi: 10.3390/antib7020015

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© 2018 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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In vitro 3D patient-derived xenograft (PDX) model. (a) GXA3067 is a HER2 overexpressing gastric tumor PDX model; (b) Size-filtered tumoroids were seeded in 384-well plates and treated with increasing concentrations of ADCs, the trastuzumab-based DAR = 8 MMAU ADC (T-MMAU ADC, upper row) and T-DM1 (Kadcyla^®, middle row); as well as the naked antibody trastuzumab (bottom row). (c) The DAR = 8 MMAU ADC was 10× more effective in reducing tumoroid size than T-DM1, while trastuzumab had only a moderate effect. (d) The DAR = 8 MMAU ADC was 18× more effective in inducing apoptosis than T-DM1, while trastuzumab did not have an effect. IC₅₀ values are marked in the figure panels and they were determined using curve fitting by nonlinear regression as the concentration of the drug that causes 50% inhibition of cell viability compared to maximum inhibition. The experiments were made with eight replicates. Error bars show the standard error of the mean.

In vitro 3D patient-derived xenograft (PDX) model. (a) GXA3067 is a HER2 overexpressing gastric tumor PDX model; (b) Size-filtered tumoroids were seeded in 384-well plates and treated with increasing concentrations of ADCs, the trastuzumab-based DAR = 8 MMAU ADC (T-MMAU ADC, upper row) and T-DM1 (Kadcyla^®, middle row); as well as the naked antibody trastuzumab (bottom row). (c) The DAR = 8 MMAU ADC was 10× more effective in reducing tumoroid size than T-DM1, while trastuzumab had only a moderate effect. (d) The DAR = 8 MMAU ADC was 18× more effective in inducing apoptosis than T-DM1, while trastuzumab did not have an effect. IC₅₀ values are marked in the figure panels and they were determined using curve fitting by nonlinear regression as the concentration of the drug that causes 50% inhibition of cell viability compared to maximum inhibition. The experiments were made with eight replicates. Error bars show the standard error of the mean.