Folate receptor alpha (FOLR1) (FOLR1)

Folate receptor alpha (FOLR1), also known as Folate Binding Protein (FBP), is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that binds folic acid and its derivatives with high affinity, facilitating their transport into cells via receptor-mediated endocytosis [UniProt: P15328]. In healthy tissues, its expression is highly restricted and localized to the apical surfaces of epithelial cells in the kidneys, lungs, and choroid plexus, making it largely inaccessible to the bloodstream [PubMed: 15141214]. However, FOLR1 is significantly overexpressed in various epithelial malignancies, particularly ovarian and lung cancers, where it contributes to tumor cell growth and survival. This differential expression profile makes it a primary target for oncology therapeutics, including antibody-drug conjugates and immunotherapies. A specific immune-mediated approach utilizes FBP-derived peptides, such as the E39 peptide, which are processed and presented by HLA-A2 molecules on the surface of cancer cells [PubMed: 21278439]. These peptide-MHC complexes are recognized by CD8+ cytotoxic T lymphocytes, providing a mechanism for vaccine-induced immune surveillance and the targeted destruction of FOLR1-positive tumor cells [ClinicalTrials.gov: NCT01580696].

Other names

Folate binding proteinFBPFolate receptor 1Adult folate-binding proteinOvarian tumor-associated antigen MOv18

Therapeutic strategies targeting FOLR1 include antibody-drug conjugates (ADCs) that deliver cytotoxic payloads upon receptor-mediated endocytosis, monoclonal antibodies that induce antibody-dependent cellular cytotoxicity (ADCC), and peptide vaccines (e.g., E39) that stimulate cytotoxic T-lymphocyte (CTL) responses against HLA-A2-presented FBP peptides on the tumor surface [PubMed: 21278439, 30333295].