Folate receptor alpha and beta (FR-alpha/beta)

Folate receptor alpha (FRα) and folate receptor beta (FRβ) are glycosylphosphatidylinositol (GPI)-anchored membrane proteins that mediate the high-affinity uptake of folate into cells via receptor-mediated endocytosis [1, 2]. FRα is highly expressed in several epithelial-derived tumors, including ovarian, endometrial, and non-small cell lung cancers, while its expression in normal tissues is limited to the apical surface of some epithelia, making it an ideal therapeutic target [1, 3]. FRβ is primarily expressed on myeloid cells and is notably upregulated on activated macrophages in inflammatory conditions like rheumatoid arthritis and on tumor-associated macrophages (TAMs) within the tumor microenvironment [2, 4]. These receptors are exploited in oncology and rheumatology through the development of antibody-drug conjugates (ADCs), radiopharmaceuticals, and folate-conjugated small molecules [3, 5]. For instance, Mirvetuximab soravtansine is an FDA-approved ADC targeting FRα for the treatment of platinum-resistant ovarian cancer [3]. Targeting FRβ offers a strategy to modulate the immunosuppressive tumor microenvironment by depleting or reprogramming TAMs [4]. [1] UniProt Consortium. Folate receptor alpha (P15328). [2] UniProt Consortium. Folate receptor beta (P14207). [3] FDA. FDA grants full approval to mirvetuximab soravtansine-gynx for FRα-positive, platinum-resistant epithelial ovarian cancer. [4] PubMed. Folate receptor beta as a target for immunotherapy (PMID: 29158374). [5] PubMed. Folate receptor-targeted therapies in cancer (PMID: 32810413).

Other names

FOLR1FOLR2Folate receptor 1Folate receptor 2Adult folate-binding proteinFetal lung folate-binding proteinPlacental folate-binding proteinFR-alphaFR-beta

Targeted delivery of cytotoxic payloads via receptor-mediated endocytosis, antibody-dependent cellular cytotoxicity (ADCC), and competitive inhibition of folate uptake.