Early Success in Curing Melanoma in Mice Spurs Mayo Vaccine Development
Success with melanoma adds to Mayo Clinic's growing portfolio of experimental cancer vaccines
19, 2012 Sixty percent of mice with melanoma skin cancer tumors were cured in less than three months by researchers at the Mayo Clinic. The
researchers trained the immune system of the mice to eradicate skin cancer from within, using a genetic combination of human DNA from melanoma
cells and a cousin of the rabies virus.
The strategy, called cancer immunotherapy, uses a genetically engineered version of the vesicular stomatitis virus to
deliver a broad spectrum of genes derived from melanoma cancer cells directly into tumors.
The mice in these early studies in Rochester, Minnesota, experienced minimal side effects, according to the report
appearing this week in the journal of Nature Biotechnology.
"We believe that this new technique will help us to identify a whole new set of genes that encode antigens that are
important in stimulating the immune system to reject cancer,. says Richard Vile, Ph.D., a Mayo Clinic researcher in the Department of
Molecular Medicine and a coauthor of the study, along with Jose Pulido, M.D., a Mayo Clinic ophthalmologist and ocular oncologist.
In particular, we have seen that several proteins need to be expressed together to generate the most effective rejection
of the tumors in mice."
Dr. Vile's success with melanoma adds to Mayo Clinic's growing portfolio of experimental cancer vaccines, which includes
an active clinical trial of vesicular stomatitis vaccines for liver cancers. Future studies could include similar vaccines for more aggressive
cancers, such as lung, brain and pancreatic.
"I do believe we can create vaccines that will knock them off one by one," Dr. Vile says. "By vaccinating against
multiple proteins at once, we hope that we will be able to treat both the primary tumor and also protect against recurrence."
The immune system functions on a seek-and-destroy platform and has fine-tuned its capacity to identify viral invaders
such as vesicular stomatitis virus. Part of the appeal of building cancer vaccines from the whole spectrum of tumor DNA is that tumors can
adapt to the repeated attacks of a healthy immune system and display fewer antigens (or signposts) that the immune system can identify.
Cancers can learn to hide from a normal immune system, but appear unable to escape an immune system trained by the
vesicular stomatitis virus with the wide range of DNA used in the library approach.
"Nobody 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."
Much immunotherapy research has slowed because of researchers' inability to isolate a sufficiently diverse collection of
antigens in tumor cells. Tumors in these scenarios are able to mutate and reestablish themselves in spite of the body's immune system.
The study was a Mayo collaboration with professors Alan Melcher and Peter Selby at the Leeds Institute of Molecular
Medicine, University of Leeds, U.K. They were also co-authors.
Other coauthors of the article are Timothy Kottke; Jill Thompson; Feorillo Galivo, Ph.D; Rosa Maria Diaz; Diana
Rommelfanger-Konkol; Elizabeth Ilett; and Larry Pease, Ph.D., all of Mayo Clinic; Hardev Pandha, M.D., University of Surrey, Guildford, U.K.;
Phonphimon Wongthida, Ph.D., Department of Virology and Cell Technology at the National Center for Genetic Engineering and Biotechnology,
Pathumthani, Thailand; and Kevin Harrington, Ph.D., Institute of Cancer Research, London, U.K.
The study was funded by the Richard M. Schulze Family Foundation, Mayo Clinic, Cancer Research UK, the National
Institutes of Health, and a grant from Terry and Judith Paul.
Melanoma is the most serious type of
cancer and senior citizens are the usual victimes. Often the first sign of melanoma is a change in the size, shape, color or feel of a mole. Most melanomas have a black or
black-blue area. Melanoma may also appear as a new mole. It may be black, abnormal or "ugly looking."
Thinking of "ABCD" can help you remember what to watch for:
● Asymmetry -
the shape of one half does not match the other
● Border - the
edges are ragged, blurred or irregular
● Color - the
color in uneven and may include shades of black, brown and tan
● Diameter -
there is a change in size, usually an increase
Melanoma can be cured if it is diagnosed and treated early. If melanoma is not removed in its early
stages, cancer cells may grow downward from the skin surface and invade healthy tissue. If it spreads to other parts of the body it can be
difficult to control.
Couples encouraged to examine each other for
suspicious moles that could be skin cancer. Researchers estimate that 40
50% of people in the U.S. who live to age 65 will have nonmelanoma
skin cancer at least once.