In their quest for smarter cancer therapies, scientists have often eyed cancer vaccines with interest. Vaccines are designed to stimulate parts of the immune system that can fight cancer. But in clinical trials, vaccines have often failed to live up to expectations. Now, a new vaccine strategy has renewed scientists' hopes: disabling one part of the immune system that cancer targets, so that other parts can fight the disease more effectively.
In humans, some cancers disable the immune system by forcing the body to make more of a class of regulatory T cells that suppress immune responses. Reducing the number of these regulatory T cells prior to administering the vaccine might boost the odds of success.
To accomplish this, Duke University urologist Johannes Vieweg, who studies kidney cancer, and his colleagues turned to a genetically engineered protein called DAB389IL-2 that's normally used to treat a form of leukemia. In cancer patients, the protein binds to the same class of regulatory T cells that lead to immune dysfunction in cancer—CD4+/CD25+ cells—and kills them. Vieweg and his colleagues reasoned that if they gave patients a dose of DAB389IL-2 before vaccinating them, that might free the body to mount a stronger immune response, thereby boosting the power of the vaccine.
Vieweg's group tested their theory on ten kidney cancer patients and one patient with ovarian cancer: Four received only the vaccine, and seven got the protein too. Those offered combination therapy generated seven times more cancer-fighting immune cells than volunteers receiving only the vaccine, the group reports in the 23 November online Journal of Clinical Investigation. "This is only one step," says Vieweg, who cautions that much larger clinical trials are needed to confirm that the strategy works. The team is now trying to keep the regulatory T cells down for a longer time after vaccination.
"The concept of eliminating" regulatory T cells prior to vaccination is smart and "clearly enhances the immune response," says oncologist Kenneth Foon of the University of Pittsburgh Cancer Institute. If refined, the technique may enhance experimental lung, prostate, and other cancer vaccines currently being tested, he adds.
— By Al Staropoli