New vaccine that inserts a vital gene into a patient’s melanoma cells shows promise against advanced stage disease
A new vaccine for use in patients
with advanced melanoma that inserts a vital gene into the patient’s
cancer cells shows promise after a 3-year follow-up of trial participants,
according to an article in the September issue of the Journal of
Clinical Oncology.
Glenn Dranoff, MD, and his American colleagues
found that 10 of 35 patients who enrolled in the vaccine study were
alive more than 3 years after the trial began and that 4 patients
had no sign of disease.
These results, which are comparable to those
obtained by Dranoff and his colleagues in earlier studies of similar
vaccines that were much harder to work with, suggest the new technique
holds real promise as a useful treatment for metastatic melanoma.
"Our findings show that an antitumor immune response to melanoma
can be created using a vaccine that is safe and relatively easy
to make," says Dranoff, the study’s senior author. "The
survival of 10 patients for more than 3 years is especially encouraging
and raises the possibility that vaccination might be effective in
combination with other, existing therapies."
In the current work, the vaccine was made
by removing a portion of a patient’s tumor and mixing the cells
with weakened adenovirus particles that carry the gene for granulocyte-macrophage
colony-stimulating factor (GM-CSF). As the virus particles invaded
the cells, the gene became inserted into the patient’s genome and
the tumor cells produced large quantities of the protein. After
the tumor cells were injected into the patient, the stimulating
factor triggered an immune response that targeted all of the melanoma
cells, not merely those carrying the inserted gene.
The study, a Phase I trial, enrolled 35 patients
with metastatic melanoma. Vaccines were successfully made for 34
patients. Of the 34 patients, 8 people withdrew from the study because
their disease progressed rapidly. Side effects of the treatment
were generally minimal, usually consisting of no more than irritation
around the injection site.
Researchers removed tumor samples from 16 patients following vaccination
to gauge the extent of tumor response. In 10 of those cases, they
found a large influx of immune system cells and substantial numbers
of dead melanoma cells on microscopic review. In addition, 10 patients
? 29 percent of the original group ? were alive 3 years after receiving
the treatment.
The results have encouraged Dranoff and his
colleagues to undertake a larger, Phase II study to test whether
the vaccine can be effective in patients with melanoma that has
not yet metastasized.
"We plan to explore alternative techniques
for producing the vaccine, as well as determining which patients
can benefit from it the most," Dranoff said. "This will
help us determine its proper place in the arsenal of melanoma treatments."
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