Abstract 5440: Activity of mesothelin-targeted immunotoxin RG7787 against triple-negative breast cancer

Abstract

Abstract Mesothelin (MSLN) is a cell surface glycoprotein normally expressed by mesothelial cells of the pleura, pericardium and peritoneum, but also highly expressed in mesothelioma, pancreatic and ovarian cancers. It was recently reported that many triple negative breast cancers (TNBCs) also express MSLN. RG7787 is a next generation, deimmunized recombinant immunotoxin (RIT) consisting of a high-affinity anti-MSLN Fab fragment for targeting, fused to a 24 kD fragment of Pseudomonas exotoxin A for cell killing. Here, we demonstrate using flow cytometry that the TNBC cell lines HCC70 and SUM149 express significant MSLN on the cell surface. HCC70 and SUM149 are sensitive to RG7787 and related RITs with IC50 values in the subnanomolar range. RG7787 has less off-target toxicity in mice than earlier mesothelin-targeted immunotoxins and could be safely administered to mice at six-fold higher doses. RG7787 shrinks HCC70 tumor xenografts grown in athymic nude mice by >40% and produces a 10 day delay in tumor progression compared to vehicle (p < 0.02). Tumor volume decreased by >85% when RG7787 was given following paclitaxel, a statistically significant improvement over paclitaxel alone. Together these data demonstrate that RG7787 has significant activity against TNBC and warrants further study as a treatment for this malignancy. Citation Format: Christine Alewine, Emily Maon-Osann, Ira Pastan. Activity of mesothelin-targeted immunotoxin RG7787 against triple-negative breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5440. doi:10.1158/1538-7445.AM2014-5440