Kinneer K, Meekin J, Tiberghien AC, Tai YT, Howard PW, Phipps S, Kiefer CM, Rebelatto MC, Dimasi N, Moriarty A, Papadopoulos KP, Sridhar S, Gregson SJ, Wick MJ, Masterson L, Anderson KC, Herbst R, Tice DA. (2018) SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads. Clin Cancer Res 24(24):6570-6582.
Objective: To develop biomarkers to uncover the underlying mechanism of resistance by certain cell lines for ADCs.
Summary: Loss of SLC46A3 expression was found to be a mechanism of innate and acquired resistance to ADCs bearing DM1 and SG3376.
Dose: For Lysosomal trafficking, ADCs were labeled with Fab-pHast human. Cells were incubated with 3 ug/mL of labeled ADCs at 37°C for desired time points. Isotype control (IgG) and 1C1-ADCs labeled with Fab-pHast were incubated with T24 and ES-2 cells for indicated time points and fluorescence quantified by flow cytometry.
Shramm PA, Ancheta L, Higgins D, Lappi DA. A rapid, pH-sensitive screening method to detect internalization of cell surface markers for development of antibody-based pharmaceuticals to treat brain tumors. Soc Neurosci Mtg, Washington DC, Abstract # 566.24, 2017. View Poster