Multivalent peptidic linker enables identification of preferred sites of conjugation for a potent thialanstatin antibody drug conjugate
Fig 1
Potency of hinge-cysteine thailanstatin trastuzumab ADC.
(A) Structure of iodoacetamide derivatized non-cleavable thailanstatin linker-payloads (LPs). (B) In vitro cytotoxicity of hinge-cysteine thailanstatin trastuzumab ADCs against cancer cell lines expressing various levels of Her2, reported in half-maximal inhibitory concentration (IC50) values of conjugated payload in nM. Data are the mean of multiple experiments. (C) In vivo efficacy of hinge-cysteine thailanstatin trastuzumab ADC1 in an N87 gastric cancer xenograft model dosed at 3 mg/kg (q4d x 4). Arrows indicate the day(s) on which intravenous dosing was carried out. DAR = Drug Antibody Ratio; 361 = MDA-MB-361-DYT2; 468 = MDA-MB-468.