Science News - May 7, 2011

A second treatment now in large clinical trials could revive fading hopes for a melanoma vaccine. At the same time, many scientists now acknowledge that vaccines probably can’t do the job alone. Two new therapies, which aren’t vaccines but do duck tumor defenses and ultimately spur on the immune system, show promise in their own right and may make natural allies for cancer vaccines.

Though the gains have yet to match many doctors’ hopes, Provenge and other immune-energizing drugs have given terminal cancer patients months of life as part of clinical trials. “That’s when you know the idea is no longer just an attractive idea,” says Glenn Dranoff, an oncologist at the Dana-Farber Cancer Institute in Boston. “Now, you have proof.”

Coley’s vaccine

The proof may be new, but the idea behind cancer vaccines is not. A New York City surgeon named William Coley was enthralled in the late 1800s by the story of a male cancer patient who came down with a severe infection, then saw his tumor shrink dramatically. Coley decided to put the power of the fever to the test, injecting cancer patients with shots of killed pathogens, including strep bacteria. The strange thing: In many patients, it worked.

“These were patients with advanced
inoperable cancer,” says epidemiologist
Stephen Hoption Cann of the University
of British Columbia in Vancouver. “They
would be considered, by and large, incur-
able by today’s standards.”
Still, Coley’s findings didn’t gain much
traction; instead radiation and chemo-
therapy became the hot treatments in
oncology. But by the 1980s and ’90s,
researchers were frustrated because
such therapies couldn’t slow many
malignant diseases. More and more
teams turned to Coley’s old battle plan.

The current thinking is that infections kick the immune system into overdrive. White blood cells go after pathogens in force, causing a lot of collateral damage to tumors in the process. Today’s proposed vaccines are better sharpshooters than Coley’s original cocktail, targeting

tumors specifically or at least limiting the damage in healthy organs. Some vaccines include whole cancer cells killed with radiation, while others contain a brew of proteins native to tumors. A few package such proteins into viruses.

To rev up the body to attack, many of these new vaccines focus on activating immune players called dendritic cells. Among other roles, these spy cells gather intelligence on potential baddies, from free-floating proteins to whole parasites. These spies return worrisome finds to a type of white blood cell called T cells. T cells, the soldier cells, then divide rapidly and go on the offensive, looking for cells or substances that match the spies’ intel.

But because cancer cells grow from normal tissue, they often look like good guys. To clue the spy cells in to big tumors, oncologists need to fix the intel.

Provenge and beyond

And that’s exactly what the team that designed the cancer vaccine Provenge did. Doctors prepare the vaccine cocktail by taking dendritic cells and similar immune players directly from a patient and mixing them with proteins that sit atop prostate cells, says Philip Kantoff, an oncologist with Dana-Farber. The mixture goes back into the patient’s bloodstream where, scientists think, the dendritic spies present the prostate proteins to immune soldier cells. That convinces the immune system to treat the prostate cells as an enemy, like it would a common virus. Vaccine researchers had previously tried this strategy and a range of others with little success. But Provenge differed from the long list of misfires in one key respect: “It actually worked,” Kantoff says.

In a Phase III trial— a large, controlled study, often the last step before FDA approval— Kantoff and his colleagues dosed 330 prostate cancer patients with customized versions of Provenge. The team also treated 167 patients with a placebo. Patients received traditional therapies before and after vaccine treatment.