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June 1, 1998

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Vaccine Kills Spreading Cancer In Animal Model

Johns Hopkins scientists have developed a vaccine that, in mice, can alert the immune system to the presence of stray cancer cells and significantly reduce their blood-borne spread.

"Metastatic cancer, or cancer that is spreading from its site of origin, is among the toughest stages of cancer to treat," says Hongxiu Ji, M.D., postdoctoral fellow. "Our findings suggest cancer vaccines could be an important tool for preventing and treating the spread of cancers."

Giving the vaccine prior to a tail vein injection of cancer cells prevented development of metastatic lung tumors in eight of 10 mice, while all the mice in two control groups that received cancer cells but no vaccine developed tumors. A second test against established lung cancer showed that the vaccine completely eliminated tumors in 50 percent of mice.

Ji presents her results, funded by the National Institutes of Health and the Richard W. TeLinde endowment, at this week's meeting of the American Society of Gene Therapy in Seattle.

The vaccine takes advantage of a protein, E7, produced by the human papilloma virus and commonly found in cervical cancers and their metastatic cancers. To make the vaccine, scientists altered vaccinia, a common virus, to include a gene for E7 and a molecular signal. The vaccine infects cells in the body, causing them to make E7, and the molecular signal triggers a chain reaction that calls E7 to the immune system's attention. This leads to an immune system attack on all cells that contain the protein--including the cancer cells.

To test whether the vaccine is effective against metastatic cervical cancer, Ji and her colleagues developed a line of tumor cells by genetically altering mouse lung cells to include E7. This made the cells similar to cervical cancer cells. She then showed that a tail vein injection of the cancer cells could cause lung tumors in mice in two weeks.

Tests showed the vaccine could prevent this process in a significant portion of the mice tested and that it could eliminate already established lung tumors.

"Ji's results demonstrate the potency of the vaccine and give hope that immunotherapy may help us control metastatic cancers," says T.C. Wu, M.D., Ph.D., associate professor of pathology. "The strategy we've used to develop this vaccine can also be used for other virus-associated cancers and any cancer that expresses a unique protein not found elsewhere in the body."

The principle disadvantage to the current vaccine, Ji notes, is that it may not be possible to use a second time in the same patient. Researchers believe that one exposure will sensitize the immune system to vaccinia, leading it to sweep up a second dose before it can infect cells and start the chain reaction.

Scientists currently are working on new approaches to overcome this problem, including direct administration of the E7 gene with a gene gun, so-called "naked" DNA vaccination. Plans also are being made for an initial human trial of the current vaccine.

Other study authors were Wu, Edwin Chang, Ken-Yu Lin, Robert Kurman, and Drew Pardoll.

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