Vaccines prevent disease by priming the immune system to recognize and attack invading germs. In theory, a similar approach could be used to fight another threat: cancer.

But as appealing as the concept sounds, therapeutic cancer vaccines have essentially defied developers, even as some other immunotherapy technologies have taken off.

Thomas Jefferson University researcher Scott A. Waldman believes that an intestinal protein called GCC, or guanylyl cyclase C, will be a cancer vaccine breakthrough.

Waldman, his colleague Adam Snook, and their team have developed a GCC-based vaccine that worked impressively — in mice — to  wipe out metastatic colon cancer. In humans, the vaccine has gotten over only the first low hurdle, demonstrating safety in 10 early-stage colon cancer patients and eliciting  signs of an immune response in half of them.

Although the nascent vaccine  has a long way to go, last month it got a vote of confidence: Korea-based Alpha Holdings Inc. announced that it is investing $8.7 million in the next phase of human testing.  The money will be used by Viral Gene Inc., a company set up to shepherd the experimental therapy through the federal drug approval process. Viral Gene sub-licensed the vaccine technology from Targeted Diagnostics & Therapeutics, Inc., the Exton-based biotech company that holds exclusive rights to the innovation.

Waldman, who has no financial stake in either company, explained that the ultimate goal is to use the vaccine after conventional treatment — surgery and perhaps chemotherapy — to mop up cancer cells that escape the primary tumor and travel to distant organs. Those aggressive but undetectable rogues are the reason that half of colorectal cancer patients ultimately wind up dying of metastatic disease.

"This is for patients who are ostensibly free of disease but they have pockets of malignant cells somewhere in their body," he said.

Waldman has spent his career deciphering the puzzle of GCC, a protein with properties that make it ideal for a vaccine strategy.

GCC is part of a complex gene-signaling pathway that regulates intestinal cell growth, thereby suppressing cancer. Normally, GCC is found on the surface of cells lining the inside of the intestines.

The researchers have used mice to identify conditions that impair GCC signaling, including obesity and irritable bowel syndrome. If GCC signaling is completely silenced, intestinal cells begin growing abnormally, sometimes progressing to tumors.

But even when cells turns malignant — and even when a few manage to escape the intestine — they carry the silenced GCC. Indeed, Waldman said, the cell produces more and more of the protein to try to restore its function.

The vaccine, given as a shot, involves genetically engineering a disarmed cold virus so that it produces GCC once it invades cells in the body. The immune system sees this GCC as a foreign marker, or antigen, and assaults any GCC-laden cells — including metastases — that are outside the intestines.

Why doesn't the attack extend to healthy GCC-carrying cells in the intestines?

"The lining of the intestines has a different immune system than the rest of the body, and those two systems don't talk to one another," Waldman said. "You can activate one compartment without activating the other one. So we're exploiting that immunological compartmentalization."

This compartmentalization overcomes an obstacle that has stymied cancer vaccines and other immunotherapy approaches: finding an antigen to safely target. Cancer cells have many of the same antigens as healthy cells — after all, malignant cells were once normal — so an immune strike can have unanticipated  "off-target" effects that are toxic, even lethal.

Still, in its first small test, the GCC vaccine slammed into another well-known barrier. Five of the 10 colon cancer patients' immune systems perceived the vaccine's harmless cold virus as an invader and wiped it out before it could make GCC. The researchers are now considering possible solutions, including a higher dose of the vaccine, for the next phase of testing.

Colon cancer, which will be diagnosed in 95,000 people in the United States this year, is the second-leading  cancer killer in this country and the world, according to the National Cancer Institute.

But the next test of the vaccine, to begin in 2017, is expected to enroll patients who have been treated for pancreatic or esophageal cancer, Waldman said. Like colon cancer, these less common cancers arise from gastrointestinal cells and, it turns out, carry GCC. Unlike most colon cancers, these others are notoriously and rapidly lethal.

"We'd know pretty quickly if the vaccine has efficacy," Waldman said.