Anti-EGFR antibody-drug conjugate for triple-negative breast cancer therapy

Yingnan Si, Yuanxin Xu, Jia Shiung Guan, Kai Chen, Seulhee Kim, Eddy S. Yang, Lufang Zhou, Xiaoguang Margaret Liu

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Triple-negative breast cancers (TNBCs) are highly aggressive, metastatic and recurrent. Cytotoxic chemotherapies with limited clinical benefits and severe side effects are the standard therapeutic strategies, but, to date, there is no efficacious targeted therapy. Literature and our data showed that epidermal growth factor receptor (EGFR) is overexpressed on TNBC cell surface and is a promising oncological target. The objective of this study was to develop an antibody-drug conjugate (ADC) to target EGFR+ TNBC and deliver high-potency drug. First, we constructed an ADC by conjugating anti-EGFR monoclonal antibody with mertansine which inhibits microtubule assembly via linker Sulfo-SMCC. Second, we confirmed the TNBC-targeting specificity of anti-EGFR ADC by evaluating its surface binding and internalization in MDA-MB-468 cells and targeting to TNBC xenograft in subcutaneous mouse mode. The live-cell and live-animal imaging with confocal laser scanning microscopy and In Vivo Imaging System (IVIS) confirmed the TNBC-targeting. Finally, both in vitro toxicity assay and in vivo anti-cancer efficacy study in TNBC xenograft models showed that the constructed ADC significantly inhibited TNBC growth, and the pharmacokinetics study indicated its high circulation stability. This study indicated that the anti-EGFR ADC has a great potential to against TNBC.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalEngineering in Life Sciences
Volume21
Issue number1-2
DOIs
StatePublished - Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Engineering in Life Sciences published by Wiley-VCH GmbH

Keywords

  • antibody-drug conjugate
  • epidermal growth factor receptor
  • targeted therapy
  • triple-negative breast cancer

ASJC Scopus subject areas

  • Bioengineering
  • Biotechnology
  • Environmental Engineering

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