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DURHAM, N.C. -- Chemotherapy given in conjunction with
cancer vaccines may boost the immune system's response,
potentially improving the effectiveness of this promising type
of cancer therapy, according to a study by researchers in the
Duke Comprehensive Cancer Center.

"Chemotherapy first knocks out T regulatory cells that
suppress immune function and we speculated that this might have
a complementary effect when used in conjunction with vaccines,
which work by boosting immune function," said Timothy Clay,
Ph.D., a researcher at Duke and a lead investigator on this
study. "We tested this theory both pre-clinically and in
patients who were part of a vaccine trial at Duke for
gastrointestinal cancers, and found that our hypothesis seemed
to be true."

The researchers will present their findings in an oral
session at the annual American Society of Clinical Oncology
meeting in Chicago, on May 31. The study was funded by the
National Cancer Institute.

Researchers used a drug called denileukin diftitox (ONTAK)
for this study; the drug is routinely used to treat a type of
lymphoma and is known to deplete certain types of immune cells
including the T regulatory cells that "put the brakes" on
immune function. They speculated it might facilitate better
immune responses to a cancer vaccine.

"In the lab work, we definitely saw a heightened immune
response when we used the denileukin diftitox in conjunction
with the vaccine. The vaccine we used targets a protein found
in gastrointestinal tumors and works by boosting immune
response to the cells carrying that protein," Clay said. "From
there, we gave the drug to 15 patients in a phase I study using
the vaccine."

The researchers found that when multiple doses of the
denileukin diftitox were given, immune response to the vaccine
was enhanced in these patients.

"This is encouraging. The next step will be to develop
better drugs that support vaccines by enhancing the immune
response they depend on to work," Clay said. "It's a concept
that can be applied to any type of solid tumor, which has huge
implications for cancer research."

Vaccines are being used in clinical trials across the
country to treat many malignancies, including lung cancer,
brain tumors and colorectal cancer.

Other researchers involved in this study include Amy
Hobeika, Takuya Osada, Delila Serra, Donna Niedzwiecki, H. Kim
Lyerly and Michael Morse.