Sep. 19, 2005 ROCHESTER, Minn. -- A Mayo Clinic research team has devised a new virus-based gene therapy delivery system to help fight cancer. Researchers say their findings will help overcome hurdles that have hindered gene therapy cancer treatments.
The Mayo research team, which includes a collaborator from the United Kingdom, describes its new approach in the current edition of Nature Medicine (http://www.nature.com/nm/index.html).
The approach relies on "therapeutic hitchhikers" -- particles derived from retroviruses (RNA-containing viruses that incorporate into the genomes of infected cells and then produce a therapeutic gene). The viral particles attach to a specific kind of T cell in the immune system and "hitchhike" to the tumor because T cells home in on tumors naturally; T cells are the immune system's major line of defense against tumors. By hitching a ride on the T cells, the therapeutic particles can hit their tumor target while avoiding detection (and destruction) by the immune system. When the Mayo team experimented with the 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 this approach," explains Richard Vile, Ph.D., Mayo Clinic molecular immunologist and lead researcher of the investigation. "Our work is an important contribution to the maturation of the field of gene therapy because ultimately treating cancers by gene therapy depends on scientists' ability to specifically target tumor cells in the patient -- and this specific-delivery feature has eluded researchers for a variety of reasons. But by devising a way for viruses to hitch rides on antigen-specific T cells, we've been able to get over multiple obstacles to gene therapy."
Dr. Vile emphasizes that the work is still experimental and not yet ready for use in human patients. But if larger studies validate these findings, the therapeutic hitchhiker approach may be employed in clinical trials of new treatments.
Significance of the Mayo Research
The Mayo investigators have invented a simpler method for using modified viruses to transport therapeutic genes to tumors. They are the first to exploit traits of retroviruses during the infection process of a cell in which attachment to the cell can occur in a nonspecific way. This opens up new opportunities for using viruses therapeutically because this method of attachment allows researchers not only to target particular cells, but also to more easily gain entry into the cells -- which they must do to deliver therapeutic genes to destroy tumors. The T cells also help kill tumors.
About the Investigation
Using mice, the Mayo Clinic team showed that retrovirus particles could successfully attach to the surface of primary T cells and then safely hitchhike -- be carried through the bodies of mice that had fully functioning immune systems and evade detection by the immune system -- to reach tumors, the sites of T cell accumulation. They further showed that once it reached the tumor, the viral transporter successfully transferred a gene to both mouse and human tumor cells that then infected the cells. This proved that the concept works.
Collaboration and Support
In addition to Dr. Vile, the Mayo Clinic research team included Caroline Cole, Ph.D.; Jian Qiao, M.D., Ph.D.; Timothy Kottke; Rosa Maria Diaz, Ph.D.; Atique Ahmed; Luis Sanchez-Perez; Gregory Brunn, Ph.D.; and Jill Thompson. John Chester, M.B.B.S., Ph.D., collaborated from the Cancer Research UK Clinical Center, St. James' University Hospital, Leeds, UK. The work was supported by grants from Mayo Foundation and the National Institutes of Health.
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