A Clue To Cancer

Hernan Acevedo is not a big name in cancer research. From his laboratory at Pittsburgh's Allegheny-Sing-er Research Institute, the 70-year-old biochemist has spent two decades pursuing the eccentric notion that all malignancies are the work of a single hormone called hCG, or human chorionic gonadotropin. Healthy adult cells are typically free of hCG. But developing embryos seem to use it to shield themselves from immune attack, and Acevedo believes malignant tumors use it for the same purpose. Other scientists haven't paid much attention to his work, but it's getting harder and harder to ignore. This week the journal Cancer is publishing the strongest evidence to date that, as Acevedo puts it, "the hormone that gives us life also kills us." And some clinicians are now exploring the possibility that a vaccine against hCG will provide a new weapon against tumors. "I don't think [the anti-hCG vaccine] is nirvana," says Stanford-based immunologist Edwin Rock. "But in terms of controlling cancer, it may be as close as we ever get."

No one doubts that hCG is critical to sustaining pregnancy. Its main role is to block menstruation and stimulate release of the hormones that prepare the uterus for occupancy. But it may do more than that. To a woman's immune system, the emergence of an embryo can come as bad news, for its cells contain the father's alien genes as well as her own. When embryonic cells are covered with hCG, they acquire a strong negative charge. Because immune cells are also negatively charged, they and the embryo repel each other like matched pairs of magnets. Eventually, the genes responsible for hCG production shut down, making way for the child's immune system to eliminate cells that become damaged or diseased.

Acevedo believes that when a mature cell becomes cancerous, it reverts to a perverse embryonic state. It divides uncontrollably while churning out hCG to keep the immune system at bay. Though cancer cells have many ways of manipulating their environments, Acevedo's research suggests that hCG may be a tumor's ultimate weapon. In past studies, he and his collaborators have recovered key portions of the hCG molecule from 78 malignant cell lines. Researchers have also found that hCG levels rise as tumors become more advanced, and that the highest levels occur in the aggressive cells that break free of established tumors to take root in other tissues.

What Acevedo hadn't established until now is that cancer cells actually produce the stuff themselves. He and his colleagues recently reanalyzed 28 of the malignant cell lines they'd studied in the past. This time they looked not for hCG itself but for signs of activity in the genes governing production of the hormone. According to the report they're publishing this week, the relevant genes were active in every sample.

Most experts are still only mildly impressed. Cancer cells may well produce hCG, says Dr. Pentti Siiteri of the University of California, San Francisco--but no one has shown that hCG plays any particular role in the disease. Dr. Drew Pardol of Johns Hopkins agrees, saying there's "no direct evidence that hCG is important" in malignancy. Dr. John White of the National Cancer Society calls the study "very promising." But he wants to see the findings replicated with tumor cells taken directly from patients, since life in a culture dish can change a cell's behavior.

But rather than wait for more lab results, a handful of researchers are trying to make clinical use of the hCG findings. In preliminary studies, they're immunizing cancer patients against hCG with a vaccine that Dr. Vernon Stevens of Ohio State University developed as a contraceptive. It consists of a small piece of the hCG protein, grafted to a molecule that reliably provokes an immune response. Vaccines like Stevens's can promptly demolish newly formed embryos by depriving them of hCG. The question is whether such vaccines will have the same effect on tumors. Animal studies have yielded encouraging results. And in a human safety study, Ohio State University oncologist Dr. Pierre Triozzi found that cancer patients produced antibodies to hCG, without noxious side effects, when treated with Stevens's formula.

With backing from the California-based Immunotherapy Corp., two research teams are now preparing to test the vaccine's therapeutic effects in people with tumors of the colon or pancreas. If everything goes perfectly, says Triozzi, the vaccine could hit the market within three years. Because hCG isn't restricted to any particular tumor type, a successful vaccine could prove equally effective against a wide range of malignancies. And unlike many of the high-tech treatments researchers are now studying, an hCG vaccine would be cheap and simple to use. People at high risk could even use it as a preventive measure. "With luck," says Rock, of Stanford, "this approach could reduce the death rate from cancer by 30 percent." That, of course, is still a fantasy. But should it come true, Hernan Acevedo will be a big name indeed.

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