Mayo Clinic Cancer Center has opened a new Phase I clinical trial testing 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," says Angela Dispenzieri, M.D., hematologist and lead researcher on the multiple myeloma clinical trial in the measles virus investigation. "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 shepherded the research from basic laboratory science to therapies being tested today 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 constructed by inserting additional genes into the measles vaccine strain.

Many cancers, including multiple myeloma, overexpress a protein, CD46, which allows them to evade 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 nearby tumor cells and fusing them together, increasing cancer cell death.

This study differs 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 which 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 exploited as a target in cancer therapy because it can concentrate radioactive iodine, thus providing a way to selectively irradiate cancer cells, image the tumors and monitor regression.

Eligible candidates for the multiple myeloma study will be adults with relapsed or refractory (that is, having had more than one type of treatment fail them) myeloma. They must not have had allogeneic (from another person) stem cell transplants and must either have had a prior measles infection or been vaccinated against it.

In the 1970s, measles infections were observed 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., Mayo Clinic Cancer Center's Molecular Medicine Program began investigating it. 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," says 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 using the measles virus against ovarian cancer reports early evidence of activity against the cancer, as well as demonstrated safety. The team can now move to administration of higher and potentially even more potent viral doses. The glioblastoma multiforme trial, which opened in the fall, is testing the safety of another strain of the measles virus for treatment, one that also enables biological monitoring of anti-tumor activity.

Dr. Russell's team also is looking at ways to use the measles virus to combat other cancers, including breast, pancreatic and liver cancer.

Funding for the investigation came from the National Cancer Institute and the Harold W. Siebens Foundation. Other Mayo Clinic Cancer Center researchers participating in the multiple myeloma project include Gregory Wiseman, M.D.; Val Lowe, M.D.; Morie Gertz, M.D.; David Kallmes, M.D.; and Mark Federspiel, Ph.D.

Disclosure: In accordance with the Bayh-Dole Act of 1980, Mayo Clinic owns equity in and has licensed this and other modified measles vaccine strains, manufacturing and uses thereof to Houston Pharma Corporation and will receive royalties from that license. Drs. Russell and Federspiel are inventors of the technology used in this research.

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