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Mesothelin-targeted immunotoxin R205 has activity against triple negative breast cancer

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • C.C. Alewine
  • I. Pastan


Mesothelin (MSLN) is a cell surface glycoprotein normally expressed by mesothelial cells of the pleura and peritoneum and known to be aberrantly expressed in mesothelioma, pancreatic adenocarcinoma and epithelial ovarian cancer. It was recently reported that a significant proportion of triple negative breast cancers (TNBCs) also express MSLN. R205 is a next generation recombinant immunotoxin (RIT) consisting of a high-affinity anti-MSLN antibody fragment for targeting, fused to a 24 kD fragment of Pseudomonas exotoxin for cell killing. Here, we demonstrate using flow cytometry that the TNBC cell lines HCC70 (7.31 X 10^3 sites/ cell) and SUM149 (1.57x10^4 sites/ cell) express significant MSLN on the cell surface and are sensitive to R205 and related RITs with IC50s in the low pM range. RIT treatment of HCC70 xenografts grown in athymic nude mice results in greater than 60% decrease in tumor volume and a 19 day delay in tumor progression (p < 0.003). Together these data demonstrate that R205 has significant activity against MSLN-expressing TNBC as a single agent in vitro and in a mouse model.

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