GM-CSF acts like a magnet for agents of the immune system, drawing an attack on melanoma cells throughout the body, not just those that contain the GM-CSF gene. When tumor samples from vaccinated patients are viewed under a microscope, cancer-fighting cells are often found swarming around the melanoma cells evidence of a potent immune response.
When the technique was first tested in melanoma patients, Dranoff and his colleagues used a retrovirus (whose genetic programming is written in RNA rather than DNA) as the delivery vehicle for GM-CSF. While the results were encouraging, the process of preparing the vaccine was both lengthy and cumbersome. The retrovirus enters only cells that are actively dividing and could itself increase the risk of cancer. Vaccines prepared in this fashion therefore require extensive safety testing before being injected into patients.
The vaccine used in the new study, by contrast, was made with a weakened cold virus, known as an adenovirus, as the gene-ferrying agent. Adenoviruses are capable of entering resting cells and produce fewer complications than retroviruses.
The study, a Phase I trial undertaken to assess the vaccine's safety and potential effectiveness, involved 35 patients with metastatic melanoma, a type of cancer that begins in the skin but which, if spread to other parts of the body, carries a high death rate. Vaccines were successfully made for all but one of the patients. Eight patients had to withdraw from the study because their disease progressed rapidly. Side effects of the treatment were generally minimal, usually amounting to no more than irritation around the injection site.
Researchers removed tumor samples from 16 patients following vaccination to gauge the extent of the tumor response. In 10 of those cases, they found a large influ
Contact: Bill Schaller
Dana-Farber Cancer Institute