| RRC ID |
65429
|
| Author |
Nagai T, Furusho Y, Li H, Hasui K, Matsukita S, Sueyoshi K, Yanagi M, Hatae M, Takao S, Matsuyama T.
|
| Title |
Production of a High-affinity Monoclonal Antibody Reactive with Folate Receptors Alpha and Beta.
|
| Journal |
Monoclon Antib Immunodiagn Immunother
|
| Abstract |
Folate receptors α (FRα) and β (FRβ) are two isoforms of the cell surface glycoprotein that binds folate. The expression of FRα is rare in normal cells and elevated in cancer cells. Thus, FRα-based tumor-targeted therapy has been a focus area of laboratory research and clinical trials. Recently, it was shown that a significant fraction of tumor-associated macrophages expresses FRβ and that these cells can enhance tumor growth. Although FRα and FRβ share 70% identity in their deduced amino acid sequence, a monoclonal antibody (MAb) reactive with both receptors has not been developed. A MAb that can target both FRα-expressing cancer cells and FRβ-expressing tumor-associated macrophages may provide a more potent therapeutic tool for cancer than individual anti-FRα or anti-FRβ MAbs. In this study, we developed a MAb that recognizes both FRα and FRβ (anti-FRαβ). The anti-FRαβ specifically stained trophoblasts and macrophages from human placenta, synovial macrophages from rheumatoid arthritis patient, liver macrophages from cynomolgus monkey and common marmoset, and cancer cells and tumor-associated macrophages from ovary and lung carcinomas. Surface plasmon resonance showed that the anti-FRαβ bound to soluble forms of the FRα and FRβ proteins with high affinity (KD=6.26×10(-9) M and 4.33×10(-9) M, respectively). In vitro functional analysis of the anti-FRαβ showed that this MAb mediates complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis of FRα-expressing and FRβ-expressing cell lines. The anti-FRαβ MAb is a promising therapeutic candidate for cancers in which macrophages promote tumor progression.
|
| Volume |
34(3)
|
| Pages |
181-90
|
| Published |
2015-6-1
|
| DOI |
10.1089/mab.2014.0072
|
| PMID |
26090596
|
| MeSH |
Animals
Antibodies, Monoclonal / biosynthesis
Antibodies, Monoclonal / immunology*
Antibody Formation
Antibody-Dependent Cell Cytotoxicity
Arthritis, Rheumatoid / diagnosis*
Arthritis, Rheumatoid / immunology
Cells, Cultured
Female
Flow Cytometry
Folate Receptor 1 / immunology*
Folate Receptor 2 / immunology*
Humans
Immunoenzyme Techniques
Lung Neoplasms / diagnosis*
Lung Neoplasms / immunology
Macaca fascicularis
Macrophages / immunology*
Mice
Ovarian Neoplasms / diagnosis*
Ovarian Neoplasms / immunology
Placenta / immunology
Pregnancy
Rats
Rats, Wistar
Surface Plasmon Resonance
T-Lymphocytes, Cytotoxic / immunology
Trophoblasts / immunology*
|
| Resource |
| Human and Animal Cells |
JFP-J1(RCB2309) |
