A human antibody against human endothelin receptor type A that exhibits antitumor potency

Man Seok Ju, Hye Mi Ahn, Seong Gu Han, Sanghwan Ko, Jung Hyun Na, Migyeong Jo, Chung Su Lim, Byoung Joon Ko, Yeon Gyu Yu, Won Kyu Lee, Youn Jae Kim, Sang Taek Jung

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Endothelin receptor A (ETA), a class A G-protein-coupled receptor (GPCR), is involved in the progression and metastasis of colorectal, breast, lung, ovarian, and prostate cancer. We overexpressed and purified human endothelin receptor type A in Escherichia coli and reconstituted it with lipid and membrane scaffold proteins to prepare an ETA nanodisc as a functional antigen with a structure similar to that of native GPCR. By screening a human naive immune single-chain variable fragment phage library constructed in-house, we successfully isolated a human anti-ETA antibody (AG8) exhibiting high specificity for ETA in the β-arrestin Tango assay and effective inhibitory activity against the ET-1-induced signaling cascade via ETA using either a CHO-K1 cell line stably expressing human ETA or HT-29 colorectal cancer cells, in which AG8 exhibited IC50 values of 56 and 51 nM, respectively. In addition, AG8 treatment repressed the transcription of inhibin βA and reduced the ETA-induced phosphorylation of protein kinase B and extracellular regulated kinase. Furthermore, tumor growth was effectively inhibited by AG8 in a colorectal cancer mouse xenograft model. The human anti-ETA antibody isolated in this study could be used as a potential therapeutic for cancers, including colorectal cancer.

Original languageEnglish
Pages (from-to)1437-1448
Number of pages12
JournalExperimental and Molecular Medicine
Issue number9
Publication statusPublished - 2021 Sept

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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