Humanized anti-CD271 monoclonal antibody exerts an anti-tumor effect by depleting cancer stem cells.
Cancer Lett
; 461: 144-152, 2019 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-31325530
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 (hCD271â¯mAâ¯b). hCD271â¯mAâ¯b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KDâ¯=â¯1.697â¯×â¯10-9â¯M). In vitro, hCD271â¯mAâ¯b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271â¯mAâ¯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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
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Neoplasias Hipofaríngeas
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Receptores de Fator de Crescimento Neural
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Anticorpos Monoclonais Humanizados
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Neoplasias Pulmonares
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Melanoma
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Citotoxicidade Celular Dependente de Anticorpos
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão