Abstract 2902: Antibody-drug conjugate targeting c-kit/CD117 suppresses imatinib resistant cancer cells

Abstract

Abstract c-Kit(CD117) is a type III receptor tyrosine kinase that mediates cell proliferation, survival, and differentiation. Gene amplification of c-kit is found in various cancers, including, glioblastoma (GBM) low grade glioma(LGG), gastrointestinal stromal tumor (GIST), sarcoma, melanoma, and small cell lung carcinoma (SCLC), leading to poor prognosis. In addition, the activation of c-kit as a cancer stem cell marker induces resistance of anti-cancer drug by increasing the expression of ABCG2. Imatinib is a first generation RTK inhibitor targeting BCR-ABL, c-kit, and PDGFR and currently using for the treatment of various cancers. Of note, the activating mutation of c-kit is found in various cancers, leading to resistance of imatinib. In this study, we have generated a human antibody targeting c-kit and developed antibody-drug conjugate using SMCC-DM1 to assess the therapeutic efficacy in vitro and in vivo. Citation Format: Jin-Ock Kim, Kwang-Hyeok Kim, Sang Gyu Park. Antibody-drug conjugate targeting c-kit/CD117 suppresses imatinib resistant cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2902.