Mayo Clinic Researchers Invent 'Hitchhiking' Viruses As Cancer Drug Delivery System

The Mayo research team, which includes a collaborator from theUnited Kingdom, describes its new approach in the current edition ofNature Medicine (http://www.nature.com/nm/index.html).

The approach relies on "therapeutic hitchhikers" -- particlesderived from retroviruses (RNA-containing viruses that incorporate intothe genomes of infected cells and then produce a therapeutic gene). Theviral particles attach to a specific kind of T cell in the immunesystem and "hitchhike" to the tumor because T cells home in on tumorsnaturally; T cells are the immune system's major line of defenseagainst tumors. By hitching a ride on the T cells, the therapeuticparticles can hit their tumor target while avoiding detection (anddestruction) by the immune system. When the Mayo team experimented withthe hitchhiking approach in mice using human and mouse cancer cells,they observed significant cure rates of metastatic -- or spreading --tumors.

"Any clinical situation in which cells home to disease sites --such as inflammation or autoimmune disease -- might benefit from thisapproach," explains Richard Vile, Ph.D., Mayo Clinic molecularimmunologist and lead researcher of the investigation. "Our work is animportant contribution to the maturation of the field of gene therapybecause ultimately treating cancers by gene therapy depends onscientists' ability to specifically target tumor cells in the patient-- and this specific-delivery feature has eluded researchers for avariety of reasons. But by devising a way for viruses to hitch rides onantigen-specific T cells, we've been able to get over multipleobstacles to gene therapy."

Dr. Vile emphasizes that the work is still experimental and notyet ready for use in human patients. But if larger studies validatethese findings, the therapeutic hitchhiker approach may be employed inclinical trials of new treatments.

Significance of the Mayo Research

The Mayo investigators have invented a simpler method for usingmodified viruses to transport therapeutic genes to tumors. They are thefirst to exploit traits of retroviruses during the infection process ofa cell in which attachment to the cell can occur in a nonspecific way.This opens up new opportunities for using viruses therapeuticallybecause this method of attachment allows researchers not only to targetparticular cells, but also to more easily gain entry into the cells --which they must do to deliver therapeutic genes to destroy tumors. TheT cells also help kill tumors.

About the Investigation

Using mice, the Mayo Clinic team showed that retrovirusparticles could successfully attach to the surface of primary T cellsand then safely hitchhike -- be carried through the bodies of mice thathad fully functioning immune systems and evade detection by the immunesystem -- to reach tumors, the sites of T cell accumulation. Theyfurther showed that once it reached the tumor, the viral transportersuccessfully transferred a gene to both mouse and human tumor cellsthat then infected the cells. This proved that the concept works.

Collaboration and Support

In addition to Dr. Vile, the Mayo Clinic research team includedCaroline Cole, Ph.D.; Jian Qiao, M.D., Ph.D.; Timothy Kottke; RosaMaria Diaz, Ph.D.; Atique Ahmed; Luis Sanchez-Perez; Gregory Brunn,Ph.D.; and Jill Thompson. John Chester, M.B.B.S., Ph.D., collaboratedfrom the Cancer Research UK Clinical Center, St. James' UniversityHospital, Leeds, UK. The work was supported by grants from MayoFoundation and the National Institutes of Health.