The study, to be published online on April 1 in the Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org), tested the effect of a single injection of the antibody MDX-CTLA4 in nine patients who had previously been treated with cancer vaccines for either metastatic melanoma or metastatic ovarian cancer. The result, in every patient who had received a particular kind of vaccine, was widespread death of cancer cells and an increase in the number of immune system cells within the tumors evidence of a potent immune system attack.

"This study makes a strong case that combined immunotherapy consisting of a vaccine and antibodies can elicit a potent immune response to some types of tumors in patients," says the study's senior author, Glenn Dranoff, MD, of Dana-Farber.

The technique was inspired by the laboratory work of study co-author James Allison, PhD, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. He and his colleagues discovered that a protein, or antigen, called CTLA-4 on T cells restrains the immune system from attacking cancer cells. In a series of laboratory and animal experiments, Allison's team showed that combining a cancer vaccine with an antibody able to block CTLA-4 resulted in an especially potent immune attack on tumors.

On the basis of those findings, Dranoff and his colleagues launched a Phase I clinical trial of the technique in a small group of patients. Because animal experiments had indicated that giving MDX-CTLA4 in combination with a vaccine might prompt the immune system to attack some normal cells, researchers decided to give the ant
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
1-Apr-2003