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To overcome TKI resistance, an anti\u2010c\u2010Kit antibody\u2013drug conjugate was developed in this study to treat wild\u2010type and mutant c\u2010Kit\u2010positive cancers. NN2101, a fully human IgG1, was conjugated to DM1, a microtubule inhibitor, through\n                    <jats:italic>N<\/jats:italic>\n                    \u2010succinimidyl\u20104\u2010(\n                    <jats:italic>N<\/jats:italic>\n                    \u2010maleimidomethyl) cyclohexane\u20101\u2010carboxylate (SMCC) (to give NN2101\u2010DM1). The antitumor activity of NN2101\u2010DM1 was evaluated\n                    <jats:italic>in\u2009vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    using various cancer cell lines. NN2101\u2010DM1 exhibited potent growth\u2010inhibitory activities against c\u2010Kit\u2010positive cancer cell lines. In a mouse xenograft model, NN2101\u2010DM1 exhibited potent growth\u2010inhibitory activities against imatinib\u2010resistant GIST and SM cells. In addition, NN2101\u2010DM1 exhibited a significantly higher anti\u2010cancer effect than carboplatin\/etoposide against SCLC cells where c\u2010Kit does not mediate cancer pathogenesis. Furthermore, the combination of NN2101\u2010DM1 with imatinib in imatinib\u2010sensitive GIST cells induced complete remission compared with treatment with NN2101\u2010DM1 or imatinib alone in mouse xenograft models. These results suggest that NN2101\u2010DM1 is a potential therapeutic agent for wild\u2010type and mutant c\u2010Kit\u2010positive cancers.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.13084","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T15:47:43Z","timestamp":1629301663000},"page":"1290-1308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A novel anti\u2010c\u2010Kit antibody\u2013drug conjugate to treat wild\u2010type and activating\u2010mutant c\u2010Kit\u2010positive tumors"],"prefix":"10.1002","volume":"16","author":[{"given":"Jin\u2010Ock","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy Ajou University Suwon\u2010si Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang\u2010Hyeok","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy Ajou University Suwon\u2010si 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