Live attenuated Edmonston strain measles virus (MV) has promising anti-tumor activity against a variety of human cancers and three phase I clinical trials evaluating the safety of intraperitoneal, intratumoral or intravenous delivery of MV are in progress at Mayo Clinic Rochester.  

However, most patients are immunized against measles virus and have anti-viral antibodies that can inactivate the virus. This limits our ability to use measles virus in metastatic diseases that require intravenous infusion of the virus. Since measles virus naturally spreads in white cells during natural infection, we propose to use cells as vehicles to carry the virus to the tumor sites. In this way, the virus is protected from undesirable elements in the circulation and can still effectively infect tumor cells and kill them. 

In this grant, we will identify the optimal protocol to load various types of cell carriers with viruses and test them in animal models. In the end, we hope to have a feasible and effective clinical protocol based on our findings to treat relapsed multiple myeloma.

Studies in recent years have documented the lytic effects of various viruses on many human cancers, and the study and re-engineering of oncolytic viruses is intensifying. Recombinant measles viruses [MV] appear to be ideal vectors for lymphoma treatment, as wild-type MV infection occasionally induces lymphoma regression in humans.  

We plan to produce viruses that replicate selectively in transformed lymphocytes, viruses with modulatable cytotoxicity, and viruses with a targeted envelope. Eventually we will combine the characteristics of the most effective viruses into a ‘second generation’ virus that is armed and targeted.