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.”
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.
War on cancer though
approaches vary, the aim of
cancer vaccines is to provoke
the body to attack tumor cells.
specific flags, or antigens,
sit atop tumor cells.
scientists mix those flags with
a person’s own spy cells.
the spy cells, sometimes
dendritic cells, take up the flags.
the activated spy cells are
injected back into the body.
the spy cells display the flags,
alerting the body’s t cells.
the t cells proliferate and
attack cancer cells.