Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells

Shinkichi Morita, Mai Mochizuki, Kouichi Wada, Rie Shibuya, Mao Nakamura, Kazunori Yamaguchi, Tomoko Yamazaki, Takayuki Imai, Yukinori Asada, Kazuto Matsuura, Kazuo Sugamura, Yukio Katori, Kennichi Satoh, Keiichi Tamai

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10−9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.

Original languageEnglish
Pages (from-to)144-152
Number of pages9
JournalCancer Letters
Volume461
DOIs
Publication statusPublished - 2019 Oct 1
Externally publishedYes

Keywords

  • Antibody therapy
  • Antibody-dependent cellular toxicity
  • CD271
  • Hypopharyngeal cancer
  • Melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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