Ravi V. J. Chari

TL;DR: In vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers are determined andtrastuzuab-MCC-DM1 shows greater activity compared with nonconjugated trastumab while maintaining selectivity for HER2-overexpressing tumor cells.

TL;DR: The antitumor activity of these targeted agents was superior to that of the antibodies alone or the standard anticancer drugs in human tumor xenograft models and opens the door to the future development of highly potent drugs that were too toxic on their own to be therapeutically useful.

TL;DR: How the lessons learned from the first-generation ADCs have led to improvements in every aspect of this technology, i.e., the antibody, the cytotoxic compound, and the linker connecting them, leading to the current successes are described.

TL;DR: These maytansinoids are linked to antibodies via disulfide bonds, which ensures the release of fully active drug inside the cells, and show high antigen-specific cytotoxicity for cultured human cancer cells, low systemic toxicity in mice, and good pharmacokinetic behavior.

TL;DR: In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study.