Abstract 537: Antibody drug conjugate to treat triple negative breast cancer

Triple negative breast cancer (TNBC) is characterized by rapid growth, metastasis, and high recurrence. The severe adverse effects and drug resistance associated with standard cytotoxic chemotherapies minimize their clinical benefits. The anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) had been developed and tested to treat TNBC, but no significant efficiency was demonstrated in clinical trials. The goal of this study was to develop a novel antibody-drug conjugate (ADC) to treat TNBC. Specifically, we established a platform to conjugate anti EGFR mAb with mertansine, which inhibits cell division by blocking tubulin polymerization, and also improved the conjugation efficiency by optimizing the linker and drug-to-antibody ratio. Flow cytometry and live cell confocal laser scanning microscopy analysis confirmed that the anti-EGFR ADC can specifically bind to multiple TNBC subtypes, is effectively internalized, and release potent drug intracellularly within 1 hour after mixing. The IC50 study showed that the anti-EGFR ADC killed >90% TNBC cells with dose of 5 nM. The TNBC xenograft mouse model also showed that the constructed ADC had high anticancer efficacy and successfully inhibited tumor growth. Moreover, the live-animal imaging using In Vivo Imaging System and the tissue microarray samples with immunohistochemical analysis of TNBC and organs indicated that our ADC specifically target TNBC in vivo. Further evaluations, such as maximal tolerated dose (MTD), pharmacokinetics (PK), and biodistribution, are needed. To summarize, we developed an EGFR-targeted ADC, which could provide an effective targeted therapy to treat TNBC and improve the life quality and survival rate of patients with TNBC. Note: This abstract was not presented at the meeting. Citation Format: Yingnan Si, Nghi Dang, Seulhee Kim, Lufang Zhou, Xiaosi Han, Runhua Liu, Xiaoguang (Margaret) Liu. Antibody drug conjugate to treat triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 537.