RRC ID 76959
Author Morita S, Mochizuki M, Wada K, Shibuya R, Nakamura M, Yamaguchi K, Yamazaki T, Imai T, Asada Y, Matsuura K, Sugamura K, Katori Y, Satoh K, Tamai K.
Title Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells.
Journal Cancer Lett
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.
Volume 461
Pages 144-152
Published 2019-10-1
DOI 10.1016/j.canlet.2019.07.011
PII S0304-3835(19)30407-0
PMID 31325530
MeSH Animals Antibodies, Monoclonal, Humanized / immunology Antibodies, Monoclonal, Humanized / pharmacology* Antibody-Dependent Cell Cytotoxicity* Apoptosis Cell Proliferation Female Humans Hypopharyngeal Neoplasms / drug therapy* Hypopharyngeal Neoplasms / immunology Hypopharyngeal Neoplasms / metabolism Hypopharyngeal Neoplasms / pathology Lung Neoplasms / drug therapy* Lung Neoplasms / immunology Lung Neoplasms / metabolism Lung Neoplasms / pathology Melanoma / drug therapy* Melanoma / immunology Melanoma / metabolism Melanoma / pathology Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / immunology Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Nerve Tissue Proteins / immunology* Receptors, Nerve Growth Factor / immunology* Tumor Cells, Cultured Xenograft Model Antitumor Assays
IF 7.36
DNA material Genome Network Project Human cDNA Clone IRAK090O06 (HGY036342) pEF-BOS-anti human CD271-#16 (RDB20193)