Folate hydrolase-1 (FOLH1) is a novel target for antibody-based brachytherapy in Merkel cell carcinoma

Folate Hydrolase-1 (FOLH1; prostate specific membrane antigen) is a type II transmembrane protein, luminally expressed by neovasculature of most solid tumors. J591, a monoclonal antibody (mAb), is specific to, and is effectively endocytosed after extracellular binding to, FOLH1; thus J591 is a vehicle for monoclonal antibody (mAb)-based brachytherapy in FOLH1+ cancers. We characterized FOLH1 expression in primary (p) and metastatic (m) MCC to determine its targeting potential for J591-brachytherapy. Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed on a MCC tissue section based on the physical properties of conjugated lutetium-177 (177Lu). Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. 81 MCC tumors were evaluated. All tumors demonstrated significant FOLH1+ vessels. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumors demonstrated FOLH1 neovascular expression. Monte Carlo simulation showed the highly localized ionizing tracks of electrons emitted from the targeted neovessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data for analysis. No significant differences in our limited data set were detected based on FOLH1 status, staining intensity score, or by grouping staining intensity scores for MCC specific survival or recurrence free survival. FOLH1 is expressed in most pMCC and mMCC cases, but does not appear to be prognostic. Our findings support further investigation of targeted therapy with J591-brachytherapy for the treatment of MCC.