|Molecular graphic of an adeno-associated virus--courtesy of NIH|
In news that could offer hope in the fight against cancer, an oral vaccine that uses a two-pronged attack stopped breast cancer recurrence in mice for over a year. While injectable or intravenous cancer vaccines overall are making great strides in the clinic, according to the researchers this is the first time that a cancer vaccine based on a recombinant adeno-associated virus (AAV) has been delivered orally.
The team chose AAV partly because of its long-term safety record and its effectiveness in gene therapy and partly because it can survive the powerful acids in the stomach, allowing oral delivery. It can also trigger humoral (antibody-based) and cellular immune responses, which can be a disadvantage in gene therapy but a real positive for vaccines.
The researchers dosed mice with breast cancer tumors with a vaccine based on an AAV5 (intramuscular) or AAV6 (oral) vector and expressing the neu protein, found on the surface of tumors. Both vaccines triggered both cellular and humoral immune responses and improved the survival of the mice, but the response to the oral vaccine was more robust and the mice survived longer. When the mice were rechallenged with cancer cells, the AAV6-based oral version of the vaccine protected 80% of the mice against cancer recurrences up to a year after vaccination. The study, a collaboration between the University of Cincinnati Cancer Institute and the National Institutes of Health (NIH), was published in the Nature journal Molecular Therapy.
"We have done similar studies with different virus strains that have produced an antibody response," says Jason Steel of the University of Cincinnati. "With this virus, we get both an antibody and a tumor-killer T-cell response. By combining the two mechanisms of action in one vaccine, we are creating a two-pronged immune system attack on the cancer cells that appears to be more effective."
The vaccine could have potential to protect women who have already been treated for breast cancer, or who could be at high risk of developing the disease. Further studies in prevention of other cancers, including lung cancer, are planned for this year.
Viruses aren't the only approach for oral cancer vaccines. Merck KGaA's joint venture with BB Biotech Ventures III, Vaximm Holding AG, moved its oral pancreatic cancer vaccine VXM01 into clinical trials in 2011.
- read the press release
- see the abstract