Measles Virus Used to Kill Multiple Myeloma

A new phase I clinical trial is evaluating an engineered measles virus against multiple myeloma, a cancer of the bone marrow that currently has no cure. This is the third of a series of molecular medicine studies in patients testing the potential of measles to kill cancer.

"This is the beginning of a long but exciting process,” remarked Angela Dispenzieri, M.D., hematologist and lead researcher on the multiple myeloma clinical trial in the measles virus investigation from Mayo Clinic Cancer Center (Rochester, MN, USA). "We are very hopeful that this will be a step toward helping our patients.”

Mayo Clinic Cancer Center is the only institution in the world currently pursuing using engineered measles viruses for cancer treatment. It has gathered the research from basic laboratory science to therapies being currently assessed in several tumor types, including glioblastoma multiforme (a brain tumor), recurrent ovarian cancer, and now multiple myeloma.

The measles viruses being used for these studies were created by inserting additional genes into the measles vaccine strain. Many tumors, including multiple myeloma, overexpress a protein, CD46, which allows them to avoid destruction by the immune system. Laboratory strains of measles virus seek out this protein and use it as a receptor by which to enter the cancer cells. Upon entry, the virus spreads, infecting neighboring tumor cells and binding them together, increasing cancer cell death.

This study is different from the other two open clinical trials because researchers are administering the measles virus strain intravenously, rather than directly to the tumor site. For multiple myeloma, the researchers are using a strain of measles virus that was engineered to carry an additional gene that codes for the sodium iodide symporter (NIS) protein.

NIS is produced by the thyroid where it attracts and concentrates iodine. This characteristic of the NIS protein can be utilized as a target in cancer therapy because it can concentrate radioactive iodine, thereby providing a way to selectively irradiate cancer cells, image the tumors and monitor regression.

In the 1970s, measles infections were seen to cause regression of pre-existing cancerous tumors in children. This information was noted, but nothing was done to study this phenomenon until the late 1990s, when, under the direction of Stephen Russell, M.D., Ph.D., from the Mayo Clinic Cancer Center's Molecular Medicine Program, began investigating it. From this, the current study and other related projects resulted.

"Mayo's multidisciplinary team and institutional support for cutting-edge research provide the perfect incubator for development of a therapeutic virus,” stated Dr. Russell. "We have everything we need, from basic scientists who create and test the vaccine strain to those who determine the best way to manufacture a safe biological delivery mechanism, and finally, to clinicians who understand the science and develop guidelines by which the study is conducted and correctly carried out. With this outstanding team, we can truly focus on achieving the greatest benefit for the patient.”

The Mayo team utilizing the measles virus against ovarian cancer reported early evidence of activity against the cancer, as well as demonstrating its safety. The investigators can now move to the administration of higher and potentially more powerful viral doses. The glioblastoma multiforme trial, which began in the fall of 2006, is evaluating the safety of another strain of the measles virus for treatment, one that also enables biologic monitoring of anti-tumor activity.

Dr. Russell's team also is examining ways to use the measles virus to fight other cancers, including breast, pancreatic, and liver cancers.


Related Links:
Mayo Clinic Cancer Center