scholarly journals Characterization of the Human Folate Receptor Alpha Via Novel Antibody-Based Probes

Oncotarget ◽  
2011 ◽  
Vol 2 (12) ◽  
pp. 1227-1243 ◽  
Author(s):  
Daniel J. O’Shannessy ◽  
Elizabeth B. Somers ◽  
Earl Albone ◽  
Xin Cheng ◽  
Young Chul Park ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Human Folate Receptor

MORAb-003 inhibits folate-driven growth mediated by the human folate receptor alpha

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10108-10108
Author(s):  
E. Routhier ◽  
H. Turchin ◽  
R. Patel ◽  
W. Ebel ◽  
P. Sass ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cho Cells ◽  
Cellular Proliferation ◽  
Folate Receptor ◽  
Dependent Manner ◽  
Phase I Clinical Trials ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Human Folate Receptor

10108 Background: MORAb-003 is a therapeutic humanized antibody currently in Phase I clinical trials for advanced ovarian cancer, and is directed against the human folate receptor alpha (FRα), an antigen which is highly overexpressed on the surface of the majority of ovarian cancers. Overexpression of FRα has been shown to confer a growth advantage to tumorigenic cells in vitro, under conditions of reduced folate availability. We have previously determined that MORAb-003 elicits robust antibody-dependent cellular cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC) in vitro, and is effective in mouse xenograft models of human ovarian cancer. We now show that MORAb-003 possesses novel, growth-inhibitory functions distinct from its immune effector properties. This activity can be recapitulated, using a cell-based assay to score inhibition of folate-dependent growth. Methods: Chinese Hamster Ovary (CHO) cells were engineered to express surface FRα. The cells were cultured under a low folate (< 20 nM) regimen, then re-fed medium supplemented with various concentrations (0–10 μM) of 5-methyltetrahydrofolate (5-MTF), a folate preferentially internalized by the FRα. Cellular proliferation was measured as a function of added 5-MTF, in the presence or absence of MORAb-003. Results: FRα-expressing CHO cells were found to require approximately 100-fold lower 5-MTF than a matched, non-expressing cell line. This increased proliferation could be reduced in a concentration-dependent manner by MORAb-003. Conclusions: MORAb-003 can antagonize the activity of human FRα, resulting in the loss of growth advantage conferred by overexpression of FRα under conditions which bracket physiological (10–100 nM) folate concentrations. [Table: see text]

Abstract 5745: Synthesis and characterization of a folate receptor alpha-specific ligand for distinguishing cancer tissue from sites of inflammation

2012 ◽  
Author(s):  
Balasubramaniam Vaitilingam ◽  
Venkatesh Chelvam ◽  
Sumith A. Kularatne ◽  
Scott Poh ◽  
Wilfredo Ayala-Lopez ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Synthesis And Characterization ◽  
Cancer Tissue ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Specific Ligand

A Novel Monoclonal Antibody for Detection of Folate Receptor Alpha in Paraffin-Embedded Tissues

Hybridoma ◽  
2007 ◽  
Vol 26 (5) ◽  
pp. 281-288 ◽  
Author(s):  
Amy E. Smith ◽  
Michael Pinkney ◽  
Nigel H. Piggott ◽  
Hilary Calvert ◽  
Ian D. Milton ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Folate Receptor ◽  
Folate Receptor Alpha ◽  
Receptor Alpha

T-Cell Immunity to the Folate Receptor Alpha Is Prevalent in Women With Breast or Ovarian Cancer

2006 ◽  
Vol 24 (26) ◽  
pp. 4254-4261 ◽  
Author(s):  
Keith L. Knutson ◽  
Christopher J. Krco ◽  
Courtney L. Erskine ◽  
Karin Goodman ◽  
Linda E. Kelemen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune System ◽  
T Cell ◽  
Cancer Patients ◽  
Folate Receptor ◽  
Prediction Algorithm ◽  
Amino Terminus ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Healthy Donors

Purpose Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity. Methods Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis. Results Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FRα peptide. Patients responded to an average of 3 ± 0.5 peptides, whereas healthy donors responded to 1 ± 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FRα antibodies consistent with a coordinated immune response. Conclusion These findings demonstrate that the FRα is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.

Abstract 657: Folate receptor alpha expression is associated with poor prognosis in patients with cervical cancer

2021 ◽  
Author(s):  
Shigemasa Takamizawa ◽  
Shu Yazaki ◽  
Yuki Kojima ◽  
Hiroshi Yoshida ◽  
Rui Kitadai ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Poor Prognosis ◽  
Folate Receptor ◽  
Folate Receptor Alpha ◽  
Receptor Alpha
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