Antibody therapies:


IPILIMUMAB STIMULATES THE
BODY'S T-CELLS
Ipilimumab (also known as MDX-010 or
MDX-101) is a human monoclonal
antibody  developed by Bristol-Myers
Squibb and Medarex.
The therapy  multiplies the effect of a
natural disease-fighting antibody has
extended the lives of patients with
metastatic melanoma in a large,
international clinical trial.

The Food and Drug Administration  in
March 2011 approved the first drug
shown to extend survival in people with
late-stage melanoma, the deadliest
form of skin cancer.
The drug, Bristol-Myers Squibb's
Yervoy, (also known as ipilimumab) is
a new treatment option for melanoma
patients who fail to respond to other
treatments.
The drug appears to work by blocking
a molecule that hinders the body's
ability to fight off cancer cells.
In a trial of 676 melanoma patients,
people who received ipilimumab lived
10 months on average, compared to 6
months for people not taking the drug,
according to a study published last
year. Patients taking ipilimumab were
also more likely to be alive after two
years.
A more recent trial found that
ipilumamab may also improve survival
for previously untreated melanoma
patients.
Side effects include fatigue, diarrhea,
skin and inflammation of the intestines.
More than 68,000 new cases of
melanoma were diagnosed last year in
the US, and about 8,700 died from it,
according to the National Cancer
Institute.


Patients in the phase III clinical study
who received the drug ipilimumab — a
monoclonal antibody made by
duplicating a single type of human
antibody thousands of times over —
survived for an average of 10 months
whether they received the drug alone
or in combination with a therapeutic
vaccine known as gp100, compared to
just over six months for those who
received gp100 alone, investigators
found.
The four-month difference represents
a 67 percent increase in survival time
between the two groups.

T cells (T lymphocytes) are immune
cells the play a critical role in the body’
s attack against tumors. Ipilimumab
represents the first in a new class of
cancer immunotherapies called T-cell
potentiators, which modulate the
“stop/go” signals that control T-cell
activation. By suppressing these “stop”
signals, ipilimumab allows the T-cell
response against cancer to proceed
unimpeded.

Ipilimumab specifically blocks CTLA-4,
a molecule that inhibits the activity of T
cells. Dr. Allison showed in 1995 that
CTLA-4 was a negative regulator of T-
cell responses, and hypothesized that
blocking it could lead to strong tumor
rejection. He went on to develop a
monoclonal antibody that successfully
blocks CTLA-4, and conducted the
early mouse studies confirming his
hypothesis of anti-CTLA-4-mediated
tumor regression.
According to Dr. Allison, T-cell
potentiation with ipilimumab may
eventually help patients with many
different types of cancer live longer.
“Studies have shown that the immune
system can recognize, target, and
attack many different kinds of cancer,”
Allison said, “and ipilimumab may help
to strengthen and sustain that immune
response, no matter the type of
cancer.”
There currently are no approved
medicines indicated for patients whose
melanomas return after primary
treatment. Melanoma is just the
beginning. “We can explore this new
treatment in many other kinds of
cancer, as well.



OTHER DEVELOPMENTS
T-DM1 by Roche for metastatic breast
cancer in clinical trial Phase 2;