Oncolytic measles virus for ovarian cancer therapy

The use of replicating viruses for cancer therapy holds much promise. Attenuated measles viruses (MVs) are promising experimental anticancer agents, which propagate efficiently in a broad range of human tumor cells rather than normal cells. Anti-neoplastic efficacy of MV against ovarian cancer cells in both in vitro and in vivo have been demonstrated. We have generated a trackable oncolytic MV expressing a soluble marker peptide (MV-CEA), which is currently being evaluated in a phase I dose-escalation trial involving ovarian cancer patients. Our efforts center on the optimization of MV, genetically engineering MV to infect ovarian cancer cells more specifically and to be more powerful. To minimize potential toxicity due to MV-associated immunosuppression and non-target cell infection, we have developed an MV that is fully retargeted to infect ovarian cancer cells. The interactions with its native receptors were ablated and a single-chain antibody (scFv) specific for the α-folate receptor (FR α), a target overexpressed on 90% of non-mucinous ovarian cancers, was engineered on the viral attachment protein (MV-αFR). The tropism and fusogenic activity of MV-α FR were also redirected exclusively to FR α. Additionally, we have generated MV-NIS, which is an oncolytic measles virus coding for the thyroidal sodium iodide symporter, and its propagation can be mapped by serial radioiodine imaging, which has been verified in mice ovarian cancer models. We found that these genetically engineered MVs are powerful candidates for clinical testing and warrant further investigation for therapeutic applications in ovarian cancer.