The Gene and Virus Therapy Program of the Mayo Clinic Cancer Center focuses on developing new gene-delivery systems and gene- and virus-based therapies for cancer treatment. The program conducts research on all three Mayo Clinic campuses — in Scottsdale, Ariz.; Jacksonville, Fla.; and Rochester, Minn.
Investigators in the Gene and Virus Therapy Program focus on four main areas of research:
Researchers study the biology of viruses and cells that are used to develop new gene-delivery systems and the modification of existing gene-delivery systems to enhance their potential value as virus-based anti-cancer therapies and gene-transfer agents.
The measles virus is an important area of focus. For example, investigators have discovered that the adherence junction protein nectin-4 is the third epithelial receptor for the measles virus, a finding that explains how the virus is able to enter airway epithelial cells.
Researchers also study retroviral integration and adenovirus biology to better understand the etiology of cancer and the development of virus-based anti-cancer therapies.
Immune system defenses can impede the success of virus-based anti-cancer therapies. But if the immune system can be redirected against tumor cells, it can be a powerful tool in cancer control.
Investigators are exploring viral targeting strategies that can be used to increase the safety and efficacy of gene-based anti-cancer therapies by circumventing the immune system. They are also studying how oncolytic virotherapy, a treatment in which a virus infects and destroys cancer cells, can elicit a potent anti-tumor immune response.
Preclinical and clinical pharmacology
Researchers have successfully translated a number of laboratory breakthroughs into clinical treatments. These treatments include:
- A measles virus derivative that encodes the sodium iodine symporter (MV-NIS) gene in patients with recurrent ovarian cancer, multiple myeloma, mesothelioma, and head and neck cancer
- A measles virus derivative that encodes the marker peptide carcinoembryonic antigen (MV-CEA) gene in patients with ovarian cancer and primary brain tumors or gliomas
- An adenovirus encoding NIS in patients with prostate cancer
- A vesicular stomatitis virus strain encoding interferon beta in patients with hepatocellular carcinoma.
Oncolytic viruses delivered intravenously struggle to survive in the circulation and to extravasate successfully into tumors. Investigators are studying how vectors could be chaperoned to sites of tumor growth inside protective cell carriers, such as autologous lymphocytes, monocytes, macrophages, dendritic cells, endothelial and hematopoietic progenitor cells, and mesenchymal stem cells.
An ideal cell carrier would be easy to prepare in large numbers, susceptible to infection by the oncolytic virus, capable of migrating to sites of tumor growth once infected with the oncolytic virus, and capable of surviving the viral infection long enough to release virus progeny at the target site.
The leader of the Gene and Virus Therapy Program is Evanthia Galanis, M.D.