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Senior Citizen Health & Medicine
Colorectal Cancer Patients' Immune Systems Fight
Back After Treatment with New Vaccine
Antibody cloned from unusual survivor of this form
of cancer
November 15, 2006 – British researchers have
developed a vaccine that stimulates the immune system in colorectal
cancer patients to fight the cancerous cells, according to a report in
today's issue of Clinical Cancer Research. In this study, the vaccine
was administered before and after surgery to remove the cancerous tumors
and results in stimulating the immune cell production in 70 percent of
cases. Colorectal cancer (cancer of colon or rectum) is the second
leading cause of cancer deaths in men and women and is most common among
senior citizens.
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October 23, 2006 – Medical science and technology
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"This is the first vaccine shown to stimulate TNF-alpha
– an immune-system protein that is very effective at killing cancer
cells," said Lindy Durrant, senior author of the study and professor of
cancer immunotherapy at the University of Nottingham.
The vaccine works by stimulating the patients'
immune response to generate infection-fighting white blood cells called
T cells, which in turn produce immune system proteins called cytokines
that destroy cancer cells. The antibody contained in the vaccine, called
105AD7, was cloned from a patient who survived seven years with liver
metastases from colorectal cancer, Durrant explained.
"This is very unusual as most patients die within
one year of getting liver metastases," she said. "I thought if this
antibody had helped this patient, if we could clone it, it might help
others."
105AD7 is structurally similar to CD55, a protein
that attaches to sugar molecules and is over-expressed in colorectal
cancer cells, protecting them from attack by the body's immune system.
While low levels of CD55 occur in all cells exposed to the immune
system, increased expression of the protein has been observed in
multiple types of tumors, including up to 80 percent of colorectal
cancers.
During the trial -- the largest to date looking at
105AD7 plus surgery -- 67 patients with colorectal cancer who were
scheduled for surgery to remove their primary tumor were randomly
assigned to receive either 100 micrograms of 105AD7 with a powder to
help absorb the vaccine, 105AD7 along with BCG (a bacteria used to
stimulate the immune system in cancer patients) during the first
immunization and the powder in subsequent vaccinations, or no treatment.
The patients, who had varying degrees of disease,
averaged age 66. Twenty-eight patients had colon cancer while in 39
patients the primary tumor was located in the rectum.
Patients were immunized before surgery on the day
they were recruited for the study, and again two weeks later if surgery
had not yet been performed. The vaccines were continued three, six and
12 weeks after surgery, and then at three monthly intervals up to a
maximum of 24 months after surgery.
Blood samples were collected from the patients
during recruitment, at surgery, and at the time of the three-, six- and
12-week post-operative immunizations. Additional blood samples were
acquired one month after each subsequent immunization.
Laboratory tests of the blood samples indicated
that a T-cell response against the vaccine was recorded in the majority
of patients. The responses tended to have two peaks: one following the
start of the immunization schedule and another several months later,
after additional immunizations.
About 70 percent of patients produced both TNF-alpha
and GM-CSF – a protein that stimulates white blood cell production – in
response to both the vaccine and to CD55.
"The immune responses to both the vaccine and CD55
were measurable, adding support to the use of CD55 as a target in cancer
treatment," Durrant said.
Nineteen of the patients died during the follow-up
period. Durrant and colleagues noted that the trial was not designed to
study the effect of the vaccines on survival.
Editor's Notes:
The research was supported by The Research
Foundation Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond.
The mission of the American Association for Cancer
Research is to prevent and cure cancer. Founded in 1907, AACR is the
world's oldest and largest professional organization dedicated to
advancing cancer research. The membership includes more than 24,000
basic, translational, and clinical researchers; health care
professionals; and cancer survivors and advocates in the United States
and more than 70 other countries. AACR marshals the full spectrum of
expertise from the cancer community to accelerate progress in the
prevention, diagnosis and treatment of cancer through high-quality
scientific and educational programs. It funds innovative, meritorious
research grants.
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