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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
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 Kdoi
10.1016/j.canlet.2019.07.011subject
Has Abstractpub_date
2019-10-01 00:00:00pages
144-152eissn
0304-3835issn
1872-7980pii
S0304-3835(19)30407-0journal_volume
461pub_type
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