Using a virus containing a 'library' of DNA, researchers from the University of Leeds in the U.K., working with the Mayo Clinic in the U.S., have developed a vaccine that was able to destroy prostate cancer tumors in mice, while leaving healthy tissue untouched. Because the virus contains multiple fragments of genes, the vaccine is able to produce many possible antigens thereby boosting its effectiveness. The technique could be used to create vaccines to treat a wide range of cancers, including breast, pancreatic and lung tumors.
Previous 'gene therapy' vaccine have often delivered just one gene to stimulate the body's immune system to destroy cancer cells by producing a protein, called an antigen. This triggers the production of an antibody to kill or neutralize the antigen, but the development of successful cancer vaccines has proven difficult because each tumor has specific proteins and identifying the right antigen has been challenging. It was also feared that using several genes to increase the chances of producing successful antigens would produce an immune system response that would be too much for the body to handle.
The researchers say they may have solved this problem by creating of a vaccine using a virus containing a 'library' of DNA that is therefore able to produce many possible antigens. Testing the vaccine on mice, they found that this approach didn't send the immune system into overdrive and the range of DNA meant the vaccine was able to target the tumor through many routes.
"This is the first time we've been able to use a whole library of DNA in a viral vaccine successfully," said University of Leeds Professor Alan Melcher. "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."
Because the DNA library was harvested from the same organ as the tumor, the immune system 'self-selected' the cancer antigens to respond to and didn't react against other healthy parts of the body. Additionally, the self-selection process was triggered when the vaccine was injected into the bloodstream, which is far more practical than injecting it directly into tumors inside the body.
For their study, the researchers took a library of DNA from the healthy prostate tissue of mice with prostate cancer and put it inside a vesicular stomatitis virus (VSV). When delivered into the mice in the virus, the vaccine stimulated an immune response that successfully tracked down and killed the tumor cells.
"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," says Professor Peter Johnson, chief clinician of Cancer Research UK, which funded the research.
The study by the University of Leeds researchers is published in the journal Nature Medicine.
