Ephrin receptor A10 monoclonal antibodies and the derived chimeric antigen receptor T cells exert an antitumor response in mouse models of triple-negative breast cancer

Jong-Ho Cha, Li Chuan Chan, Ying Nai Wang, Yu Yi Chu, Chie Hong Wang, Heng Huan Lee, Weiya Xia, Woei Cherng Shyu, Shih Ping Liu, Jun Yao, Chiung Wen Chang, Fan Ru Cheng, Jielin Liu, Seung-Oe Lim, Jennifer L. Hsu, Wen-Hao Yang, Gabriel N. Hortobagyi, Chunru Lin, Liuqing Yang, Dihua YuLong Bin Jeng, Mien Chie Hung

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Expression of the receptor tyrosine kinase ephrin receptor A10 (EphA10), which is undetectable in most normal tissues except for the male testis, has been shown to correlate with tumor progression and poor prognosis in several malignancies, including triple-negative breast cancer (TNBC). Therefore, EphA10 could be a potential therapeutic target, likely with minimal adverse effects. However, no effective clinical drugs against EphA10 are currently available. Here, we report high expression levels of EphA10 in tumor regions of breast, lung, and ovarian cancers as well as in immunosuppressive myeloid cells in the tumor microenvironment. Furthermore, we developed anti-EphA10 monoclonal antibodies (mAbs) that specifically recognize cell surface EphA10, but not other EphA family isoforms, and target tumor regions precisely in vivo with no apparent accumulation in other organs. In syngeneic TNBC mouse models, we found that anti-EphA10 mAb clone #4 enhanced tumor regression, therapeutic response rate, and T cell–mediated antitumor immunity. Notably, the chimeric antigen receptor T cells derived from clone #4 significantly inhibited TNBC cell viability in vitro and tumor growth in vivo. Together, our findings suggest that targeting EphA10 via EphA10 mAbs and EphA10-specific chimeric antigen receptor–T cell therapy may represent a promising strategy for patients with EphA10-positive tumors.

Original languageEnglish (US)
Article number101817
JournalJournal of Biological Chemistry
Volume298
Issue number4
DOIs
StatePublished - Apr 2022

Keywords

  • antitumor immunity
  • cancer immunotherapy
  • chimeric antigen receptor T cell
  • ephrin receptor A10
  • monoclonal antibody
  • targeted therapy
  • triple-negative breast cancer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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