British researchers have developed a vaccine that stimulates the body’s immune system to fight off cancerous cells.
In a clinical trial of 67 colorectal cancer patients, University of Nottingham
scientists found that when the vaccines were administered before and after
tumour removal surgery, immune cell production increased in 70 per cent
of the volunteers.
"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.
The vaccine worked by stimulating the immune response in the patients to
generate infection-fighting white blood cells (T cells).
T cells generate the immune system proteins, called cytokines, which destroy
cancer cells.
The active antibody ingredient in the vaccine is called 105AD7, which 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 tumours, including up to 80 per cent of colorectal cancers.
The effects of 105AD7 before and after surgery
The current trial is the largest to look at the effects of 105AD7 and surgery
to date.
The 67 colorectal cancer patients who were already scheduled for surgery
to remove the primary tumour were randomly assigned either 100 micrograms
of 105AD7, along with an adsorption powder, or 105AD7 with a BCG bacterium
to stimulate the immune system for the first immunisations.
Some participants subsequently took the powder for further vaccinations
or no treatment at all.
As the patients were in varying degrees of the disease but averaged at the
age 66, 28 of the partakers had colon cancer, while in 39 of them, the tumour
was located in the rectum.
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 high points: one following the start of
the immunisation schedule and another several months later, after additional
immunisations.
About 70 per cent 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.
These results are published in the 15 November issue of Clinical Cancer
Research.