The metabolism of Trastuzumab emtansine can be increased when combined with Abatacept. The serum concentration of Trastuzumab emtansine can be increased when it is combined with Abametapir. TargetĪ Receptor tyrosine-protein kinase erbB-2 As well, similar to trastuzumab, in vitro studies have shown that both HER2 receptor signalling inhibition and antibody-dependent cytotoxicity are mediated by trastuzumab emtansine. DM1 binds to tubulin in microtubules and inhibits microtubule function producing cell arrest and apoptosis. Lysosomes degrade trastuzumab emtansine and release DM1. Trastuzumab emtansine binds to the HER2 receptor’s sub-domain IV and goes into the cell by receptor-mediated endocytosis. Together MCC and DM1 are called emtansine and are produced by chemical synthesis. These two portions are covalently connected by 4- cyclohexane-1-carboxylate (MCC), which is a stable thioether linker. The drug portion is DM1, which is a maytansine derivative that inhibits microtubules. The antibody portion is trastuzumab, which is humanized anti-HER2 IgG1, and produced in the mammalian Chinese Hamster Ovary cells. Trastuzumab emtansine is a HER2 antibody-drug conjugate. Thus the physiological effects of trastuzumab emtansine are cell cycle arrest and cell death by apoptosis. The effect was specific for HER2-positive tumors. In this Herceptin- resistant model, tumor regrowth was observed after cessation of Trastuzumab- DM1 treatment, yet regression re-occurred when dosing was resumed. In contrast, Trastuzumab-DM1 caused >90% tumor reduction in all mice. In the Herceptin- resistant model, Herceptin alone had no effect on tumor growth. In the Herceptin-responsive models, Trastuzumab-DM1 caused complete tumor regression in all mice, whereas Herceptin alone slowed tumor growth. Trastuzumab emtansine was evaluated in two Herceptin-responsive and one Herceptin-resistant breast tumor models. Monoclonal antibody (mAb) Protein Chemical Formula Not Available Protein Average Weight Not Available Sequences Not Available Synonyms Type Biotech Groups Approved, Investigational Biologic Classification Protein Based Therapies Second that there is a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity. First that trastuzumab emtansine and trastuzumab cannot be interchanged. Trastuzumab emtansine is marketed under the brand name Kadcyla and is indicated for use in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment. T-DM1 combines two strategies- anti-HER2 activity and targeted intracellular delivery of the potent anti-microtubule agent, DM1 (a maytansine derivative)-to produce cell cycle arrest and apoptosis. Trastuzumab emtansine, formerly called Trastuzumab-DM1 (T-DM1) is a first-in-class HER2 antibody drug conjugate (ADC) comprised of Genentech's trastuzumab antibody linked to ImmunoGen's cell-killing agent, DM1. Kadcyla Generic Name Trastuzumab emtansine DrugBank Accession Number DB05773 Background

T dm1 mechanism of action