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Erschienen in: Cancer Chemotherapy and Pharmacology 1/2019

29.04.2019 | Original Article

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

verfasst von: Zhuanglin Li, Mingxue Wang, Deling Yu, Wenting Luo, Jianmin Fang, Changjiang Huang, Xuejing Yao

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2019

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

These novel antibody–drug conjugates, particularly for RC68-MC-VC-PAB-MMAE, may be a potential candidate for treatment of EGFR + NSCLC.
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Metadaten
Titel
Monomethyl auristatin E-conjugated anti-EGFR antibody inhibits the growth of human EGFR-positive non-small cell lung cancer
verfasst von
Zhuanglin Li
Mingxue Wang
Deling Yu
Wenting Luo
Jianmin Fang
Changjiang Huang
Xuejing Yao
Publikationsdatum
29.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 1/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03848-9

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