Hitchhiking Viruses Deliver Gene Therapy

They reported that this system should help in overcoming obstacles that have hindered gene therapy cancer treatments.

The researchers, from the Mayo Clinic (Rochester, MN,USA) and the Cancer Research UK Clinical Center, St. James' University Hospital (Leeds, UK), reported their new approach in the October 2005 issue of the journal Nature Medicine.

The approach focuses on "therapeutic hitchhikers,” particles taken from retroviruses (RNA-containing viruses that integrate into the genomes of infected cells and then produce a therapeutic gene). The viral particles bind to a certain type of T cell in the immune system and then hitchhike to the tumor since T cells zoom in on tumors naturally (T cells are the immune system's key line of defense against tumors). By hitching a ride on the T cells, the therapeutic particles can strike their tumor target while avoiding detection, and therefore destruction, by the immune system. When the Mayo team evaluated the hitchhiking approach in lab mice using human and mouse cancer cells, they noted considerable cure rates of metastatic tumors.

"Any clinical situation in which cells home to disease sites, such as inflammation or autoimmune disease, might benefit from this approach,” explained 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 stressed that the study is still in its early stages and not yet ready for use in human patients. But if larger studies confirm these findings, the therapeutic hitchhiker method may be used in clinical trials of new treatments.

The investigators have devised a simpler method for using engineered viruses to deliver 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 creates new avenues for using viruses therapeutically because this attachment technique allows investigators not only to target particular cells, but also to more easily gain entry into the cells, which they must do to transport therapeutic genes to destroy tumors.

Using mice models, the Mayo Clinic team demonstrated that retrovirus particles could effectively attach to the surface of primary T cells and then safely hitchhike--be transported through the bodies of mice that had fully functioning immune systems and avoid detection by the immune system--to reach tumors, the sites of T cell accumulation. They additionally 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 confirmed that the approach works.


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