Engineered measles virus as a novel oncolytic therapy against prostate cancer

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Abstract
BACKGROUND No curative therapy is currently available for locally advanced or metastatic prostate cancer. Oncolytic viruses represent a novel class of therapeutic agents that demonstrates no cross‐resistance with existing approaches and can therefore be combined with conventional treatment modalities. Measles virus strains deriving from the Edmonston (MV‐Edm) vaccine strain have shown considerable oncolytic activity against a variety of solid tumers and hematologic malignancies. In this study, we investigated the antitumor potential of recombinant MV‐Edm derivatives as novel oncolytic agents against prostate cancer. METHODS The susceptibility of prostate cancer cell lines (PC‐3, DU‐145, and LNCaP) to measles virus infection was demonstrated using an MV‐Edm derivative expressing green fluorescent protein (GFP). MV‐Edm replication in prostate cancer cell lines was assessed by one step viral growth curves. The oncolytic effect of an MV‐Edm strain engineered to express the human carcinoembryonic antigen (CEA) was demonstrated in vitro by MTT assays and in vivo in subcutaneous PC‐3 xenografts. CEA levels were quantitated in cell supernatants and mouse serum samples. RESULTS Recombinant MV‐Edm strains can effectively infect, replicate in and kill prostate cancer cells. Intratumoral administration of MV‐CEA at a total dose of 6 × 106 TCID50 resulted in statistically significant tumor growth delay (P = 0.004) and prolongation of survival (P = 0.001) in a subcutaneous PC‐3 xenograft model. Viral growth kinetics paralleled CEA production. CONCLUSIONS MV‐CEA has potent antitumor activity against prostate cancer cell lines and xenografts. Viral gene expression during treatment can be determined by monitoring of CEA levels in the serum; the latter could allow dose optimization and tailoring of individualized treatment protocols. Prostate 69: 82–91, 2009. © 2008 Wiley–Liss, Inc.