Researchers test new therapy for
advanced melanoma
Melanoma is a particularly deadly
form of skin cancer very resistant to treatment. Researchers at H.
Lee Moffitt Cancer Center & Research Institute and the University of
South Florida are testing a promising new therapy that prompts the
immune system to aid in the fight against melanoma tumors.
“This is a milestone clinical trial because it is the first time
that electroporation is being used to deliver plasmid DNA in a gene
therapy study in humans,” said Richard Heller, PhD, USF professor of
medical microbiology and immunology who helped develop the
technology used in the study.
Electroporation is a technique in
which a hand-held device applied to the skin delivers pulses of
electricity to open up pores in the tumor cell membrane. This
opening allows a small therapeutic molecule -- in this case a
molecule known as a DNA plasmid that contains the gene for
Interleukin-12 -- to slip inside the melanoma tumor before the
membrane reseals.
“Melanoma does not respond well to
standard chemotherapy,” said Adil Daud, MD, assistant professor of
oncology in the Cutaneous Oncology Program at Moffitt. “Gene therapy
gives us the flexibility to introduce a huge variety of potential
targets for treatment, but its major limitation has been getting the
gene into the cancer. If electroporation can deliver the gene to
these tumors reliably and without serious side effects, melanoma and
other cancers would be open to many new treatment possibilities.”
Six years of laboratory studies by
Dr. Heller and his colleagues preceded the initial human trial begun
earlier this year at Moffitt. The collaboration of USF and Moffitt
in this trial is a good example of translational research -- moving
the new application of a gene transfer technology from an animal
model to the patient. Dr. Heller’s team worked extensively with Dr.
Daud to adapt the electroporation technique used on mice to humans.
The researchers injected the DNA plasmid, which encodes a gene that
stimulates the immune system, directly into the tumor site in mice.
Then, they applied electroporation to the site to help the plasmid
move into the tumor cells. The tumor cells used the plasmid’s
genetic instructions to make proteins. These proteins signaled the
immune system to recognize the melanoma tumors as abnormal and
attack.
Eighty percent of the mice were
cured with this therapy -- their tumors disappeared and the treated
animals remained disease free for the full length of the study (100
days), Dr. Heller said.
Furthermore, he said, even when
melanoma cells were reinjected into the cured mice the tumors were
rejected. This indicates the immune system formed a memory response
that recognized the melanoma cells as foreign and prevented tumor
regrowth.
“We were very encouraged by the results of the preclinical studies.”
Dr. Heller said. “We’re hoping this translates into a beneficial
treatment for patients.”
The Phase 1 clinical trial by Moffitt and Genetronics Biomedical
Corp is evaluating the safety of the electroporation technology in
treating patients with advanced melanoma. The trial expects to
enroll 18 to 25 patients.
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