The concept is straightforward: beat cancer by boosting the body's defense system. Michael Mastrangelo, M.D., and his colleagues at Jefferson Medical College have inserted a gene for an immune-system enhancing protein into the tumor cells of advanced melanoma patients, using the time-tested vaccinia virus as their vaccine vehicle.

The gene encodes granulocyte macrophage colony stimulating factor, or GM-CSF, a substance which revs the body's immune reaction.

Dr. Mastrangelo, professor of medicine at Thomas Jefferson University in Philadelphia, and his colleagues have treated seven patients with advanced melanoma, with mixed results: two patients didn't respond, three had mixed responses, one had a partial response and one had a complete response. He reports his team's early results with such a vaccine at the annual meeting of the American Society of Clinical Oncology in Atlanta.

In creating an effective vaccine, Dr. Mastrangelo and his colleagues would like to make the melanoma tumor more 'immunogenic,' more likely to be noticed by the immune system. To do this, they are attempting to alter the 'cytokine milieu.'

For a tumor to evoke an immune response, substances called cytokines, which are involved in cell-to-cell communication, are required to attract cells that process tumor antigens (substances that attract attention to the immune system) and other cells that would react against the tumor. "My theory is that the key element in generating the immune response is the antigen processing," he says.

"To enhance this, you need to recruit antigen-presenting cells to the tumor site, which can be done with a cytokine, GM-CSF. This should kick off the immune response that causes tumor regression."

For GM-CSF to be manufactured at the tumor site, Dr. Mastrangelo explains, the scientists need to put the GM-CSF gene directly into the tumor cells, which then make it themselves. To do this,
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Contact: Steve Benowitz
steven.benowitz@mail.tju.edu
215-955-5291
Thomas Jefferson University
14-May-1999