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Even that, Rosenberg says, can be improved on. He is tipping the odds further in favor of the anticancer cells by genetically modifying the tumor-fighting T cells so that cancer cells aren't simply among the ones they recognize but are the only ones they recognize eliminating the distraction of other infections and allowing the T cells to devote all their energy to the malignancy alone. In June he published results showing that such manipulation can cause regression of tumors in one-third of subjects. "I think the most important progress in using the immune system is not by a vaccine but by using cell-transfer approaches," says Rosenberg. "Those are looking to be far more effective."
Measuring that effectiveness will be another challenge. The melanoma- and lymphoma-vaccine studies both tracked only the extent to which tumors regressed and were not designed to document what most cancer experts not to mention patients see as the gold standard of any new therapy: survival. Do patients who are vaccinated live longer than those who are not? How do the vaccine's cancer-controlling powers compare with those of the expanding list of drugs designed to sneak in and halt growing lesions by shutting off their supply of nutrients and oxygen or hampering their growth spurts?
Solving those riddles might be the most formidable challenge yet for the vaccine field. Some experts are already questioning the need for the lymphoma vaccine when a drug, rituximab, exists to control the disease. Kwak points out, however, that in addition to being able to seek out small deposits of tumor cells that even the best-targeted drug therapies might miss, vaccines are generally less toxic. Rituximab, for instance, can lead to viral infections and heart problems and may be toxic to the kidneys. If, as some researchers hope, cancer is ever to become more of a chronic disease like diabetes, which can be managed for life, finding treatments that are safe and effective over many years becomes critical. "The risk-benefit ratio begins to swing more against chemotherapy or targeted agents for long-term maintenance," says Kwak. "Whereas a vaccine, with a favorable safety profile, is ideal for that kind of setting."
If that's true, then this first group of cancer vaccines is well on its way to seeding an entirely new field of immune-based treatments for cancer. "In some way, shape or form, our body repairs cancer cells and 'prevents' cancer," says Lichtenfeld. "If it didn't, we would have much more cancer than we actually see. How simple it would be for us to take some markers on a cancer cell's surface and create a vaccine to help the body do what it's supposed to do." It's not simple at all, as it turns out, but it's an idea whose power and potential certainly make it worth the effort.
The original version of this article misstated that Dr. Steven Rosenberg trained Dr. Larry Kwak at the National Cancer Institute (NCI); in fact, the doctors only worked at NCI at the same time. The original article also omitted the currently held positions of Dr. Douglas Schwartzentruber and Dr. Kwak, at the Goshen Center for Cancer Care and MD Anderson Cancer Center, respectively.