A series of intravenous (IV) vaccinations with a virus carrying fragments of DNA coding for normal human prostate tissue surface antigens cured cancer in about 80 percent of mice with established prostate tumors, new study findings showed.
The study, published online June 19 in Nature Medicine, was led by Dr. Richard Vile of the Mayo Clinic in Rochester, MN, and Dr. Alan Melcher of the Cancer Research UK Clinical Centre in Leeds. If the new approach can be translated from mice to humans, such vaccines could “be readily constructed for off-the-shelf use and [could] be easily delivered” intravenously, the study authors wrote.
The researchers created the cancer vaccine by inserting an extensive “library” of DNA fragments from normal human prostate cells into a mutated form of a virus called vesicular stomatitis virus (VSV). Each VSV particle carries a different DNA fragment, and each fragment holds the code for making a particular human prostate antigen, a piece of protein capable of triggering an immune response.
When the researchers injected the virus particles intravenously into mice bearing prostate tumors, the DNA fragments, known as complementary DNAs (cDNAs) that coded for surface antigens, were translated in the mice into a wide range of human prostate antigens.
Bolstered by VSV itself, which produces a strong immune response, the antigens triggered an immune reaction that selectively targeted prostate tumor cells while sparing healthy prostate tissue and other normal mouse tissues. Injecting the vaccine directly into prostate tumors was not nearly as effective as intravenous injection and produced signs of an autoimmune response in the mice.
“By expressing all of these proteins in highly immunogenic viruses, we increased their visibility to the immune system,” Dr. Vile said in a news release. “The immune system now thinks it is being invaded by the viruses, which are expressing cancer-related antigens that should be eliminated.”
The researchers found that tumors in mice were cured more effectively with nine IV injections given every other day than with a series of three or six IV injections. Tumor cells that survived an initial round of three IV vaccinations “were readily treated by second-line virus-based immunotherapy” using DNA fragments that coded for antigens on the surfaces of resistant tumor cells, the study authors wrote.
Dr. James Gulley of NCI’s Center for Cancer Research, who studies human cancer vaccines but was not involved in the current work, said that a possible strength of the new approach “is the large number of potential antigens that can be targeted,” although he said that this might also make it harder to monitor the immune response to a similar vaccine in human studies. Dr. Gulley also noted the challenges inherent in taking promising vaccine approaches from mice into the clinic.
The method described by Dr. Vile and his colleagues is just one approach being explored in the search for effective cancer vaccines in humans, Dr. Gulley added. “I don’t think it really matters in the end what initiates an immunologically relevant killing of tumor cells,” he said. “The key is to get the immune system trained to kill the tumor cells, and it may be that multiple vaccine approaches will demonstrate similar effectiveness.”
NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute
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