Bystander killing effect of DS‐8201a, a novel anti‐human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity

• Published in: Cancer science Vol. 107; no. 7; pp. 1039 - 1046
• Main Authors: Ogitani, Yusuke, Hagihara, Katsunobu, Oitate, Masataka, Naito, Hiroyuki, Agatsuma, Toshinori
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2016; John Wiley and Sons Inc
• Subjects: Ado-Trastuzumab Emtansine; Animals; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - pharmacology; Antibody‐drug conjugate; Antigens; Antitumor activity; Antitumor agents; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Bystander Effect - drug effects; bystander killing; Camptothecin - analogs & derivatives; Camptothecin - immunology; Camptothecin - pharmacology; Cell Line, Tumor; Cell Membrane Permeability - drug effects; Cell Proliferation - drug effects; Clinical trials; Cytotoxicity; DNA topoisomerase; Drug dosages; Epidermal growth factor; ErbB-2 protein; Female; Gastric cancer; Hematology; HER2; Humans; Hypotheses; Immunoconjugates - immunology; Immunoconjugates - pharmacology; Laboratories; Lymphoma; Maytansine - analogs & derivatives; Maytansine - immunology; Maytansine - pharmacology; Mice; Mice, Inbred BALB C; Mice, Nude; Monoclonal antibodies; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - pathology; Original; Payloads; Permeability; Polymerization; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - immunology; Stomach Neoplasms - enzymology; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; Stomach Neoplasms - pathology; Targeted cancer therapy; topoisomerase I inhibitor; Topoisomerase I Inhibitors - pharmacology; Toxicity; Trastuzumab; Tumors; T‐DM; Xenografts; United States > US; Japan; topoisomerase I inhibitor; T-DM; HER2; bystander killing; Antibody-drug conjugate

Antibody–drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS‐8201a is a human epidermal growth factor receptor 2 (HER2)‐targeting antibody–drug conjugate prepared using a novel linker‐payload...