| 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
|
| Resource |
| DNA material |
Genome Network Project Human cDNA Clone
IRAK090O06 (HGY036342)
pEF-BOS-anti human CD271-#16 (RDB20193) |
