Sometimes when you're searching hard for an answer, you end up making discoveries you never anticipated. Researchers in Cell Biology Prof. John Herr's laboratory know that feeling well.
Herr's research group, funded by the University Health System, has worked with sperm proteins for 20 years with hopes of developing new contraceptives. But, as of 1999, the group also is working on another project: trying to develop a new therapy for cancer patients.
The key to the project is further researching a sperm protein named SPAN-X, a by-product of cancerous cells. Michael Coppola, a research instructor in Herr's laboratory, explained how they might use SPAN-X to diagnose and treat several types of cancer. The first step is to find out which cancer cells produce SPAN-X.
"Then you can develop a kit to look for [SPAN-X], and that may help you find cancers earlier," Coppola said.
A blood test for SPAN-X would be more convenient than conventional ways of testing for cancer, such as biopsies and CAT scans, he said. But nobody has started working on creating a blood test.
The research group already has conducted preliminary experiments that point to the usefulness of SPAN-X in diagnosing cancer.
Coppola and others in Herr's lab now are testing human cancer tissue samples for the presence of SPAN-X.
"I don't want to overstate this, but we have some exciting data that it may be present frequently in ovarian cancer," Coppola said.
Herr's laboratory also will work with Craig Slingluff, a professor of surgery in the Medical School and director of the Human Immune Therapy Center, which tries to develop new therapies for cancer patients.
Together, they hope to use the results of SPAN-X research to diagnose cancer in its early stages and give patients a new treatment option.
How it works
Immune systems in healthy people do not recognize SPAN-X as a friendly protein, so when the body sees SPAN-X, it initiates an immune response.
That means healthy people do not have antibodies to SPAN-X, which is great news for Herr's laboratory and his collaborators, who want to use this "immunological ignorance" to their advantage, Coppola said.
"We're trying to get the patients' immune systems to recognize their tumors as though they were infectious," Coppola said.
When SPAN-X proteins show up in parts of the body besides the testis gland, where they naturally occur in healthy males, "they're more likely to become targets for an immune response," he said.
Because SPAN-X is isolated from the immune system, researchers can target cancer cells without risking damage to healthy tissue, said Ann Westbrook, a research associate in Herr's laboratory who led the team that discovered the gene for SPAN-X in 1993.
In their search for a new therapy, the scientists will first make sure cancer patients' immune systems are responding to SPAN-X.
"Then we can actually think about ways of enhancing that response," Coppola said.
The researchers will also have to find out SPAN-X's function in both sperm cells and cancer cells. If SPAN-X is important to the survival of cancer cells, the team may be able to develop a drug that interferes with the protein.
Coppola said he suspects SPAN-X, a nuclear protein, may perform the same function in both kinds of cells, but he does not know what that might be.
The team also could create a vaccine that boosts cancer patients' immune response to SPAN-X. The vaccine also would target several other proteins associated with cancer.
"If you target just one protein, the tumor can escape that response," Coppola said.
The discovery
"Because the lab is always looking for testis-specific proteins to use as contraceptive targets, this protein was particularly interesting," said Westbrook, referring to the original focus of the lab's research.
It was not until 1999, six years after Westbrook's team discovered the SPAN-X gene, that the breakthrough occurred.
In late 1999, scientists at the University of Nijmegen in Holland found certain cancer cells produce a protein called CTp11, which normally resides in sperm cells.
Later, Herr's research group realized its SPAN-X sperm protein was the same as the CTp11 cancer protein. They immediately recognized the potential for a new cancer therapy.
Although developing these therapies may take many years, Coppola said, "there is good support for this approach" to fighting cancer.
"There's a lot to be learned about the right way to stimulate the immune system of a cancer patient," he added.
SPAN-X has opened up a new avenue of research for Herr's lab, he said.
"There are a lot of questions that we still have to answer regarding this," Westbrook said.
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