Mayo Clinic investigators and United Kingdom collaborators cured well-established prostate tumors in mice.
The cancer treatment approach encourages the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments. Mayo’s immunotherapy research led by Richard Vile, PhD, Mayo Clinic immunologist, and Richard M. Schulze Family Foundation professor, is a candidate for treatment of 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. 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 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.
Clinical trials could begin within two years.
The findings appear in the journal Nature Medicine.
Release Date: June 19, 2011
Source: Mayo Clinic
Filed Under: Drug Discovery