Production of a High-affinity Monoclonal Antibody Reactive with Folate Receptors Alpha and Beta.
Monoclon Antib Immunodiagn Immunother
; 34(3): 181-90, 2015 Jun.
Article
en En
| MEDLINE
| ID: mdl-26090596
ABSTRACT
Folate receptors α (FRα) and ß (FRß) 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 FRß and that these cells can enhance tumor growth. Although FRα and FRß 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 FRß-expressing tumor-associated macrophages may provide a more potent therapeutic tool for cancer than individual anti-FRα or anti-FRß MAbs. In this study, we developed a MAb that recognizes both FRα and FRß (anti-FRαß). The anti-FRαß 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-FRαß bound to soluble forms of the FRα and FRß proteins with high affinity (KD=6.26×10(-9) M and 4.33×10(-9) M, respectively). In vitro functional analysis of the anti-FRαß showed that this MAb mediates complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis of FRα-expressing and FRß-expressing cell lines. The anti-FRαß MAb is a promising therapeutic candidate for cancers in which macrophages promote tumor progression.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Artritis Reumatoide
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Trofoblastos
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Receptor 1 de Folato
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Receptor 2 de Folato
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Neoplasias Pulmonares
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Macrófagos
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Anticuerpos Monoclonales
Límite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Monoclon Antib Immunodiagn Immunother
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón