Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 61–72 | Cite as

Monomethyl auristatin E-conjugated anti-EGFR antibody inhibits the growth of human EGFR-positive non-small cell lung cancer

  • Zhuanglin Li
  • Mingxue Wang
  • Deling Yu
  • Wenting Luo
  • Jianmin Fang
  • Changjiang Huang
  • Xuejing YaoEmail author
Original Article



Epidermal growth factor receptor (EGFR) is highly expressed on non-small cell lung cancers (NSCLC) and a valuable therapeutic target. This study aimed at producing and characterizing monomethyl auristatin E (MMAE)-conjugated anti-EGFR antibody as a novel EGFR-targeting therapy for NSCLC.


A humanized anti-EGFR monoclonal antibody (named RC68) was purified and conjugated with MMAE using a MC-VC-PAB or PY-VC-PAB linker. The in vitro and in vivo antitumor activity of RC68-MC-VC-PAB-MMAE and RC68-PY-VC-PAB-MMAE were characterized.


The RC68 was generated from RC68-expressing cells and had a purity of > 99.0%. The RC68 recognized EGFR on tumor cells, particularly for higher EGFR expressing H125, A431, HCC827 and H1975 cells. The RC68 was conjugated with an average of 4 MMAE molecules to generate RC68-MC-VC-PAB-MMAE and RC68-PY-VC-PAB-MMAE, respectively. The RC68-MC-VC-PAB-MMAE, RC68-PY-VC-PAB-MMAE and RC68 displayed similar binding affinity to EGFR on tumor cells, and RC68-MC-VC-PAB-MMAE and RC68-PY-VC-PAB-MMAE were effectively internalized by H125 cells. The RC68-MC-VC-PAB-MMAE and RC68-PY-VC-PAB-MMAE inhibited the growth of H125 cells in vitro with an IC50 7.37–8.04 ng/mL and implanted H125 tumors in vivo, but did not affect body weights of mice. The antitumor effect of RC68-MC-VC-PAB-MMAE was stronger than RC68-PY-VC-PAB-MMAE, which was also stronger than docetaxel in vivo.


These novel antibody–drug conjugates, particularly for RC68-MC-VC-PAB-MMAE, may be a potential candidate for treatment of EGFR + NSCLC.


Epidermal growth factor receptor Non-small cell lung cancer Monoclonal antibody Antibody–drug conjugates 



The authors thank both Hongwen Li and Xiaoyu Xu at RemeGen Ltd. for their help in preparing RC68 antibody.


This work was supported by a Grant from the National Science and Technology Major Project of China (Grant number: 2014ZX09508004-003).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

Animal experiment was approved by Medicilon and carried out in accordance with the institutional guidelines. This study did not contain any experiment with human participants.

Supplementary material

280_2019_3848_MOESM1_ESM.docx (25 kb)
Supplementary file1 (DOCX 24 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.RemeGen, Ltd.YantaiChina
  2. 2.Mabplex International Ltd.YantaiChina
  3. 3.School of Life Science and TechnologyTongji UniversityShanghaiChina

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