Mayo Clinic investigators and collaborators from the United Kingdom cured well-established prostate tumors in mice using a human vaccine with no apparent side effects. This novel cancer treatment approach encourages the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments. Such a treatment model could some day help people to live tumor free with fewer side effects than those experienced from current therapies.
The findings appear in the journal Nature Medicine.
"We are hopeful that this will overcome some of the major hurdles which we have seen with immunotherapy cancer research," says Richard Vile, Ph.D., Mayo Clinic immunologist, Richard M. Schulze Family Foundation Professor and a lead author of the study. Clinical trials could begin within two years.
Mayo's immunotherapy research led by Dr. Vile already shows promise in treating prostate cancer and melanoma. It also is a prime candidate for treatment of many more aggressive cancers, such as lung, brain and pancreatic cancer.
Among the team's findings: no trace of autoimmune diseases in the mice. The murine T-cells attacked only cancerous prostate cells, leaving the healthy tissue unharmed.
To develop this new approach, geneticists assembled snippets of genetic code from healthy human prostate tissue into a complementary DNA (cDNA) library. These bits of cDNA were then inserted into a swarm of vesicular stomatitis viruses (VSV), which were cultured and reintroduced into the test mice as a vaccine during a series of intravenous injections.
Development of comprehensive cDNA libraries from healthy human prostate tissue represents the key to successful immunotherapy. All infections, allergens and tissues, including tumors, have a unique fingerprint called an antigen -- a molecular protein tag that triggers a response from the body's immune system. Dr. Vile deployed the human vaccine prostate cancer antigens through the mutated VSV vector to raise a full-on assault from the mice's T-cells. After exposure to the mutated viruses, the animals' immune systems recognized the antigens expressed in the virus and produced a potent immune response to attack the prostate tumors.
"Nobody really knows how many antigens the immune system can really see on tumor cells," says Dr. Vile. "By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system. The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated."
Previous attempts to vaccinate against prostate and other types of cancerous tumors have been hampered largely by researchers' inability to isolate a sufficiently diverse and robust collection of antigens in tumor cells. Because of this, tumors often mutate and re-establish themselves in spite of the body's immune system.
The use of viruses as vectors for cDNA libraries overcomes the difficulty of isolating antigens in tumor cells by giving the immune system a more complete picture of the cancerous invader.
This study was a Mayo collaboration with Alan Melcher, Ph.D., and Peter Selby, Ph.D., both from the Cancer Research UK Clinical Centre at St. James' University Hospital and professors at the Leeds Institute of Molecular Medicine, University of Leeds, UK.
Co-authors of the article are: Timothy Kottke; Jose Pulido, M.D.; Feorillo Galivo, Ph.D.; Jill Thompson; Phonphimon Wongthida, Ph.D.; and Rosa Maria Diaz, Ph.D., all of Mayo Clinic; Fiona Errington, Ph.D.; John Chester, Ph.D.; Peter Selby, Ph.D.; and Alan Melcher, Ph.D., all of the Cancer Research UK Clinical Centre, St. James' University Hospital and Leeds Institute of Molecular Medicine, University of Leeds, UK; Heung Chong, Ph.D., of St George's Hospital Medical School, London; Hardev Pandha, Ph.D., of the University of Surrey, Guildford, UK; and Kevin Harrington, Ph.D., of the Institute for Cancer Research, London.
The National Institutes of Health, Cancer Research UK, The Richard M. Schulze Family Foundation, Mayo Clinic, and a private grant funded the study.
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