Oncolytic virotherapy for targeting ovarian cancer using fully folate receptor targeted recombinant measles virus

4019 We have shown that the MV-Edm, a vaccine strain of measles virus, is potently oncolytic for many types of tumor cells but causes minimal damage on normal cells. Phase I clinical trial in ovarian cancer using recombinant measles virus which express soluble CEA for non-invasive monitoring of viral gene expression is on-going in our institution. We are continuing to improve the efficacy and specificity of oncolytic measles virotherapy for ovarian cancer. Folate receptor alpha (FR alpha) is overexpressed in 90% of ovarian cancer but is absent in most adult somatic tissues, making FR alpha an attractive tumor selective target for ovarian cancer. To generate a fully retargeted virus, measles H interaction with viral receptors CD46 and SLAM was eliminated by alanine substitution at residues 481 and 533 of measles H protein. To target virus entry and cell fusion exclusively to FR alpha ovarian cancer cells, we cloned MOv18, a scFv against FR alpha, onto measles H and rescued MV-MOv18, the fully FR alpha retargeted measles virus. MV-MOv18 specifically infected and caused extensive fusion in FR alpha expressing cells. In contrast to parental MV-GFP, MV-MOv18 showed only background infection in normal cells. Specificity of MV-MOv18 for FR alpha tumors was also demonstrated in vivo . Intraperitoneal administration of MV-GFP to measles susceptible CD46 transgenic mice resulted in the virus being trapped by peritoneal macrophages, but not MV-MOv18. These results showed that MV-MOv18 is promising oncolytic virus for ovarian cancer virotherapy.