Engineered Measles Virus as a Novel Oncolytic Therapy Against Prostate Cancer

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 turners 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 ail 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 call effectively infect, replicate in and kill prostate cancer cells. Intratumoral administration of MV-CEA at a total dose of 6 x 10(6) 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. (C) 2008 Wiley-Liss. Inc.