It
seems like an almost impossible dream — a
cancer vaccine that would protect
healthy people at high risk of cancer. Any incipient malignant cells would be
obliterated by the immune system. It would be no different from the way
vaccines protect against infectious diseases.
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However, unlike
vaccines for infectious diseases, the promise of cancer vaccines has only
dangled in front of researchers, despite their arduous efforts. Now, though,
many hope that some success may be nearing in the quest to immunize people
against cancer.
The first vaccine
involves people with a frightening chance of developing pancreatic cancer, one
of the most difficult cancers to treat once it is underway. Other vaccine
studies involve people at high risk of colon and breast cancer.
Of course, such
research is in its early days, and the vaccine efforts might fail. But animal
data are encouraging, as are some preliminary studies in human patients, and
researchers are brimming with newfound optimism.
“There is no
reason why cancer vaccines would not work if given at the earliest stage,” said
Sachet Shukla, who directs a cancer vaccine program at MD Anderson Cancer
Center. “Cancer vaccines,” he added, “are an idea whose time has come.” (Shukla
owns stock in companies developing cancer vaccines.)
That view is a
far cry from where the field was a decade ago, when researchers had all but
given up. Studies that would have seemed like a pipe dream are now underway.
“People would
have said this is insane,” said Dr Susan Domchek, the principal investigator of
a breast cancer vaccine study at the
University of Pennsylvania.
Now, she and
others foresee a time when anyone with a precancerous condition or a genetic
predisposition to cancer could be vaccinated and protected.
“It’s super
aspirational, but you’ve got to think big,” Domchek said.
A less grim
prognosis
Marilynn Duker knew her family tree was dotted with relatives who had
cancer. So when a genetic counselor offered her testing to see if she had any
of 30 cancer-causing gene mutations, she readily agreed.
The test found a
mutation in the gene CDKN2A, which predisposes people who carry it to
pancreatic cancer.
“They called and
said, ‘You have this mutation. There really is nothing you can do,’” recalled
Duker, who lives in Pikesville,
Maryland, and is CEO of a senior living
company.
She began having
regular scans and endoscopies to examine her pancreas. They revealed a cyst. It
has not changed in the past several years. But if it develops into cancer,
treatment is likely to fail.
Patients such as
Duker don’t have many options, said Dr Elizabeth Jaffee, deputy director of the
Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins University. A person
with more-advanced cysts could avoid cancer by having their pancreas removed,
but that would immediately plunge them into a realm of severe diabetes and
digestive problems. The drastic surgery might be worthwhile if it saved their
lives, but many precancerous lesions never develop into cancer if they are
simply left alone. Yet, if the lesions turn into cancer — even if the cancer is
caught at an early stage — the prognosis is grim.
But it also
offers an opportunity to make and test a vaccine, she added.
In pancreatic
cancer, Jaffee explained, the first change in normal cells on the path to
malignancy almost always is a mutation in a well-known cancer gene, KRAS. Other
mutations follow, with six gene mutations driving the cancer’s growth of
pancreatic cancer in the majority of patients. That insight allowed Hopkins
researchers to devise a vaccine that would train T cells — white blood cells of
the immune system — to recognize cells with those mutations and kill them.
Their first
trial, a safety study, was in 12 patients with early-stage pancreatic cancer
who already had been treated with surgery. Although their cancer was caught
soon after it had emerged and despite the fact that they were treated,
pancreatic cancer patients typically have a 70 percent to 80 percent chance of
having a recurrence in the next few years. When pancreatic cancer returns, it
is metastatic and fatal.
Two years later,
those patients have not yet had a recurrence.
Now, Duker and
another patient have been vaccinated to try to prevent a tumor from starting in
the first place.
“I am really
excited about this opportunity,” she said.
The vaccine seems
safe, and it has elicited an immune response against the common mutations in
this cancer.
“So far, so
good,” Jaffee said.
But only time
will tell if it prevents cancer.
Preempting a
precancer
Dr Mary Disis, director of the Cancer Vaccine Institute at the
University of Washington, wants to prevent breast cancer in women with gene
variants that put them at high risk. Her initial hopes, though, are more
modest.
One goal is to
help women who have ductal carcinoma in situ, which doctors call a precancer.
Surgery is the standard treatment, but some women also have chemotherapy and
radiation to protect themselves from developing invasive breast cancer.
“Ideally, a vaccine would replace those treatments,” she said.
She began by
looking at breast cancer stem cells. These cells, found in early cancers, are
resistant to chemotherapy and radiation, and they can metastasize. They drive
recurrences of breast cancers, said Disis, who has received grants from
pharmaceutical companies and is a founder of EpiThany, a company that is
developing vaccines.
Disis and her
colleagues found a number of proteins in these stem cells that were normal but
produced at a much higher level in cancer cells than in noncancerous cells.
That offered an opportunity to test a vaccine that produced some of those
proteins.
Their vaccine was
tested in women with advanced cancers that were well-established. It did not
cure the cancers but demonstrated that the vaccine could provide the sort of
immune response that might help earlier in the course of the disease.
Disis plans to
try vaccinating patients with ductal carcinoma in situ, or another precancerous
condition, atypical ductal hyperplasia. Her group has a vaccine they developed
to target three proteins produced in abnormally high amounts in these lesions.
The hope, she
said, is to make the lesions shrink or go away before the women have surgery to
remove them.
“This would be
proof the vaccine has a cleansing effect,” she said. If the vaccine succeeds,
women may feel comfortable forgoing chemotherapy or surgery.
To paint a grand
future
“I really think we will see a few vaccines approved for clinic in the
next five years,” Disis said. The first vaccines, she predicts, will be used to
prevent recurrences in patients whose cancer was successfully treated.
“Then, I think we
will very rapidly move on to primary prevention,” giving vaccines to healthy
people at high risk, she said.
Others are
similarly optimistic.
“At least we know
the road map,” said Dr Shizuko Sei, medical officer of the chemopreventive
agent development research group at the National Cancer Institute.
“People may
disagree, but the answer at this point is, yes, it is possible” to make
vaccines to intercept cancer, she said.
Domchek said she
can envision a future in which people will have blood tests to find cancer
cells so early that they do not show up in scans or standard tests.
“To paint a grand
future,” she said, “if we knew the tests predicted cancer, we could say,
‘Here’s your vaccine.’”
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