launched a nonprofit, AliveAndKickn, to
promote research and awareness of Lynch
syndrome, which affects an estimated
1.1 million people in the United States.
“There is a lot of anxiety in this patient
population,” says oncologist and geneticist
Eduardo Vilar-Sanchez of the MD Ander-
son Cancer Center. “It is a big psycho-
logical burden.” In hopes of easing that
strain, Vilar-Sanchez will soon lead a clini-
cal trial of a vaccine to prevent or at least
delay Lynch-related cancers. If it works,
Dave Dubin says, “it could be huge.”
Vaccines to prevent certain types of
cancer already exist. They target viruses:
hepatitis B virus, which can trigger liver
cancer, and human papillomavirus, which
causes cervical and some other cancers.
But most cancers are not caused by viruses.
The Lynch vaccine trial will be one of the
first clinical tests of a vaccine to prevent
nonviral cancers.
The idea is to deliver into the body bits
of proteins, or antigens, from cancer cells
to stimulate the immune system to attack
any incipient tumors. The concept isn’t
new, and it has faced skepticism. A decade
ago, a Nature editorial dismissed a promi-
nent breast cancer advocacy group’s goal
of developing a preventive vaccine by 2020
as “misguided,” in part because of the ge-
netic complexity of tumors. The editorial
called the goal an “objective that science
cannot yet deliver.” But now, a few teams—
including one funded by the same advocacy
group, the National Breast Cancer Coali-
tion (NBCC)—are poised to test preven-
tive vaccines, in some cases in
healthy people at high genetic
risk for breast and other can-
cers. Their efforts have been
propelled by new insights into
the genetic changes in early
cancers, along with the rec-
ognition that because even
nascent tumors can suppress
the immune system, the vac-
cines should work best in
healthy people who have never had cancer.
Researchers are trying out several vac-
cine strategies. Some use so-called tumor
antigens, molecular markers that are
scarce on healthy cells but plentiful on
cancer cells. The Lynch vaccine instead
targets “neoantigens,” a potent type of
antigen only found on tumor cells. Some
deploy just a single antigen whereas oth-
ers use a large number, in a bid to broadly
shield against cancer. The best approach is
unclear, and developers also face the dif-
ficult challenge of measuring success with-
out waiting decades for healthy people to
develop cancers.
Early trials are yielding glimmers of
promise. If the idea works to prevent one
or a few cancers, it could be extended to
meet an ambitious goal suggested by Presi-
dent Joe Biden: developing a vaccine that
could prevent many types of cancer, mod-
eled on the messenger RNA (mRNA) vac-
cines that have helped fight the COVID-19
pandemic. “We are a long way from a gen-
eral vaccine” to prevent cancer, says medi-
cal oncologist Shizuko Sei of the National
Cancer Institute’s Division of Cancer Pre-
vention. “But it could be in the distant fu-
ture. It’s a stepwise approach.”EFFORTS TO HARNESS the immune system
to fight cancer have a long history. In the
1890s, physician William Coley reported
that injections of bacterial toxins—a vac-
cine of sorts—sometimes shrank patients’
tumors, apparently by stimulating the im-
mune system. Decades later, researchers
discovered that immune cells called T cellscould recognize tumor antigens as foreign
and attack cancers. This finding led to two
classes of approved therapies: drugs that
lift molecular brakes on T cells so they can
intensify their anticancer attack, and T
cells engineered to home in on cancer cells.
Both kinds of treatment have had striking
success against certain cancers.
A third type of immunotherapy, vaccines
to treat cancer, has lagged. Efforts took off
in the early 1990s, when researchers be-
gan to tally dozens of tumor antigens that
might rouse a patient’s immune defenses.
Often these antigens are proteins that
cancer cells use to grow or spread, so the
antigens are good markers of
cancer cells.
But despite promising data
from animal experiments,
most treatment vaccines failed
to halt tumor growth in peo-
ple. Because tumor-associated
antigens can also be pres-
ent in scant quantities on
normal cells, the immune
system tends to ignore them.
The chemotherapy or other harsh treat-
ments cancer patients receive also weaken
their immune response, and tumors are
protected by their “microenvironment”—
surrounding cells and molecules that sup-
press killer T cells and block them from
entering tumors. The only approved treat-
ment vaccine, for advanced prostate can-
cer, extends life by just 4 months.
Some scientists thought cancer vaccines
might work better to prevent rather than
treat the disease. One proponent was Uni-
versity of Pittsburgh cancer immunologist
Olivera Finn, whose team in 1989 discov-
ered the first tumor-associated antigen: a
version of MUC1, a sugar-laden cell-surface
protein. The altered version dots many
types of cancer cells.
Finn developed a vaccine consisting of
short stretches of MUC1. In the first study
of a preventive vaccine in healthy people,
she tested safety in 39 people who had
previously had precancerous colon polyps,
which put them at elevated risk for colon
cancer. In 2013, her team reported 17 had
a strong immune response, with much
higher levels of antibodies to the tumor
version of MUC1 than previously seen in
cancer patients who got the vaccine as
treatment. The other 22 people, who didn’t
make antibodies, had immune-suppressing
cells in their blood, apparently lingering
from their removed polyps, Finn says.
The trial’s modest success led to a larger,
placebo-controlled trial to see whether the
vaccine prevented new polyps in people
who had had them removed. This time,
just 11 of 53 participants who receivedNEWSSCIENCE science.org 8 APRIL 2022 • VOL 376 ISSUE 6589 127
Zach Dubin (left) and Dave Dubin
hope for vaccines that could
prevent cancer in families like theirs.“We’re inspired
because the
impact will
be massive.”
Robert Vonderheide,
Penn Medicine