Worldwide, 1.6 million new cases of breast cancer
are diagnosed each year, leading to over 0.5 million deaths
40 years ago in the UK
the 5 year survival rate following diagnosis of breast cancer was 50%
today that figure is 80% thanks to advances in treatment and
screening.
One of these advances is Herceptin
a breast cancer drug that reduces the chance of the cancer coming back by
over a third. Herceptin was developed using rats
mice, hamsters and macaques. Herceptin was the first monoclonal antibody
used to successfully treat cancer. Antibodies are a type of protein
produced by the immune system that attach tightly to a specific target
Herceptin is designed to attach to a protein
known as a HER2. HER2 makes cancer cells grow and replicate faster
Herceptin prevents HER2 from working properly
and causes the cancer cells to die. However,
this only works for patients whose cancer has a high level
of HER2 protein, these are known as
HER2 positive cancers and make up around
1 in 5 breast cancers. Herceptin was originally just used to treat breast
cancer in its later stages
but is now applied to early-stage breast cancer as well
the HER2 protein was discovered in 1982
in neurological tumors of rats. In 1985
the first monoclonal antibodies to target against HER2 in mice
showed they could reduce tumor growth and prolong survival
In 1987 researchers showed
that high levels of HER2 in women with breast cancer
are linked with a lower survival rate this meant a monoclonal antibody
could work in humans just as it did in mice. To develop an antibody treatment to
target HER2
researchers begin by injecting HER2 into a mouse
the mouse's immune system then tries to get rid of the HER2 protein
by developing antibodies against it. Antibodies are y-shaped molecules
that specifically target foreign material in our bodies
the B-cells that manufacture these antibodies
were extracted from the mouse's spleen. These cells like all healthy cells
have a limited life span, this means that they cannot be grown in the lab for long
enough
to produce sufficient antibodies for medical testing. To get around this
the spleen cells were fused with special human myeloma cells
these myeloma cells can replicate indefinitely
and are regularly used by scientists for research
the fused cells are called hybridomas
once a sales have grown enough they are screaned
to find a cell that produces an antibody targeting HER2 specifically
this is the hallmark of monoclonal antibodies
they are produced from a single original cell
this means that there is no mixture of different types of antibodies
and so all of the antibodies given to the patient will work in the same way,
reducing side effects
if a mouse antibody is given directly to humans, it can trigger an immune reaction
this is because the human immune system
recognizes that it is foreign. To avoid this
the genes for producing the Herceptin antibody are altered
to make Herceptin more human-like. Herceptin is made by DNA that is 95 %
human
and 5% mouse, this is enough to trick the immune system into thinking
that it is human and so ignoring it
but it keeps the important HER2 targeting section from the mouse
at the tips of the antibody so it can bind to HER2
the newly humanize gene for the antibody
is then placed inside ovary cells taken from Chinese hamsters
a common set of cells used in research these cells can be grown in
unlimited amounts and the antibodies are extracted from them
and given to patients. Herceptin was developed in 1991
but before it could be tested in humans it was important to understand how Herceptin
behaves in a living system
monkeys and mice were used to check if Herceptin was safe and to look for dangerous
side effects
studies in Cynomolgus monkeys showed that Herceptin can pass through to
embryos
or foetuses in pregnant patients and can also pass through to breast milk in
nursing mothers
this means that Herceptin is not routinely recommended for women
who are pregnant or breastfeeding
since 1998 Herceptin has been given to more than 1.3 million patients worldwide
research continues to make it easier to administer the drug
in September 2013 a new formulation of Herceptin was approved in Europe
that allows it to be given to patients by injection which takes about 5
minutes
previously it was administered by intravenous drip
a process that can take up to 90 minutes