New therapy for Advanced Melanoma
By University of South Florida Health Sciences Center
Apr 6, 2005, 18:57
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."
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