June 20, 2011

Researchers Making Headway With Cancer Vaccines

Researchers from the Mayo Clinic along with collaborators from the United Kingdom have cured well-established prostate tumors in mice using a human vaccine with no apparent side effects.

Encouraging new cancer treatments are allowing the immune system to rid itself of prostate tumors without assistance from toxic chemotherapies and radiation treatments. A standardized treatment such as this could someday help people to be cured of cancer free while experiencing fewer side effects than those from current therapies.

Lead researcher for Mayo's immunotherapy program, Richard Vile, Ph.D., is observing promise in treating prostate cancer and melanoma. The treatments are also primed to treat many more aggressive cancers, such as lung, brain and pancreatic cancer.

The scientists are finding no trace of autoimmune diseases in the mice. The murine T-cells attacked only cancerous prostate cells, leaving the healthy tissue unharmed.

In developing these fresh approaches, 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.

Scientists have also tried to boost the effectiveness of vaccines by using several genes to increase the chances of producing successful antigens. But a worry has always been that the immune system's response would be too strong for the body to handle.

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."

University of Leeds Professor Alan Melcher, co-author of the study, explains, "This is the first time we've been able to use a whole library of DNA in a viral vaccine successfully.

"The biggest challenge in immunology is developing antigens that can target the tumor without causing harm elsewhere. By using DNA from the same part of the body as the tumor, inserted into a virus, we may be able to solve that problem."

The vaccine was made by putting the DNA library inside a vesicular stomatitis virus (VSV), which stimulates an immune response that can then track down and kill tumor cells.

Professor Peter Johnson, Cancer Research UK's chief clinician, says, "This is an interesting and significant study which could really broaden out the field of immunotherapy research."

"Although the vaccine didn't trigger the immune system to overreact and cause serious side effects in mice, it will need to be further developed and tested in humans before we can tell whether this technique could one day be used to treat cancer patients."

The findings appear in the journal Nature Medicine.


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