FRα (FOLR1) is expressed on epithelial tumor cells — ovarian, endometrial, NSCLC — and is the primary target for anti-FRα ADCs. FRβ (FOLR2) is expressed on activated macrophages, including tumor-associated macrophages (TAMs), and is a separate therapeutic target for macrophage-directed therapies. Anti-FRα therapeutic antibodies must demonstrate selectivity over FRβ to ensure tumor-cell-directed killing. When testing antibody candidates, include both FOLR1 and FOLR2 recombinant proteins in your binding panel.

In normal tissues, FOLR1 is expressed on the apical (luminal) surface of polarized epithelial cells — specifically in kidney proximal tubules, choroid plexus, and lung. Tight junctions prevent circulating antibodies from reaching the apical surface. In tumors, epithelial polarity is lost, exposing FOLR1 on the basolateral surface accessible to blood-borne antibodies. This anatomical inaccessibility in normal tissues — combined with high tumor expression — creates a wide therapeutic window for anti-FRα ADCs.

For Mirvetuximab soravtansine, FRα expression is scored by IHC using the PS2+ scoring method: staining intensity (0, 1+, 2+, 3+) × percentage of positive cells, with a threshold of ≥75% of cells at ≥2+ intensity defining "FRα-high" status. Only FRα-high patients are eligible for treatment. Different anti-FRα clinical programs may use different scoring algorithms, so confirm the specific companion diagnostic criteria for your study.

Soluble FRα is shed from the tumor cell surface by GPI-anchor cleavage. Elevated serum sFRα levels are associated with advanced ovarian cancer and may act as an antigen sink — binding circulating anti-FRα therapeutic antibodies before they reach the tumor, potentially reducing efficacy. Our FOLR1 ELISA kit can measure sFRα in serum to assess this risk and to monitor sFRα as a pharmacodynamic biomarker during treatment.

The highest FOLR1 expression is seen in high-grade serous ovarian cancer (70-80% of cases are FRα-positive), followed by endometrial cancer, NSCLC (especially adenocarcinoma), triple-negative breast cancer, and mesothelioma. FRα expression is generally low or absent in colorectal, gastric, and hematologic malignancies. IHC screening is recommended to confirm FRα positivity before including tumor models in anti-FRα drug development programs.