PANVAC Vaccines
Pancreatic cancer is
an extremely aggressive type of cancer, causing most of the affected patients to
succumb to the disease in a short period of time, since early diagnostics is
not available, and when cancer is identified, it might be too late for the
successful recovery for the disease. Current standard cancer treatments such as
surgery, chemotherapy and radiotherapy are not effective against this disease
as this is a treatment unmanageable disease. The lifetime risk of
developing pancreatic cancer is about one in 76 for both men and women and
there is a five-year survival rate of only five percent, despite advancements
in surgery, chemotherapy and radiation treatment.
Therefore, general vaccination approach as the promising treatment strategy is currently under investigation in multiple research centers. What used to be a relatively esoteric line of research – immunotherapy for cancer -- has become mainstream. In fact, there are so many companies and institutions involved in various aspects of cancer vaccine research that the Albert B. Sabin Vaccine Institute has organized the Cancer Vaccine Consortium to help accelerate the development and licensure of these immunotherapies. Some biotech firms have been investigating cancer vaccines for decades now, and the lessons they've learned over time inform the burgeoning field as it moves forward.
Therefore, general vaccination approach as the promising treatment strategy is currently under investigation in multiple research centers. What used to be a relatively esoteric line of research – immunotherapy for cancer -- has become mainstream. In fact, there are so many companies and institutions involved in various aspects of cancer vaccine research that the Albert B. Sabin Vaccine Institute has organized the Cancer Vaccine Consortium to help accelerate the development and licensure of these immunotherapies. Some biotech firms have been investigating cancer vaccines for decades now, and the lessons they've learned over time inform the burgeoning field as it moves forward.
Beginning 2004, Cambridge, Mass.-based Therion Biologics Corporation submitted
its application to the FDA to conduct a Phase III trial under a special
protocol assessment, the company prepared published data of 12 different
randomized pancreatic cancer trials.
"Median survival of that group was three months, no matter what the
agent used was," said Mark Leuchtenberger, president and CEO of Therion.
"Unfortunately, I think what we've done is just confirm those data right
now."
The Phase III trial, begun in May 2004, enrolled 255 patients with
advanced pancreatic cancer and was aiming to show a 50 percent improvement -
about a two-month extension - in survival over control chemotherapy. The study
was designed from two Phase I studies that showed a median overall survival of
more than six months.
Panvac-VF is designed to stimulate the immune system to target anddestroy
cancer cells expressing carcinoembryonic antigen and mucin-1, which are found
on more than 90 percent of pancreatic tumor cells. The vaccine incorporates
Therion's triad of co-stimulatory molecules (B7.1, ICAM-1 and LFA-3) to enhance
and sustain a targeted immune response.
However, the trial was NOT successful, and the expected positive outcomes
for the patients have not been proven.
Vaccine Direct Injection in Pancreatic Tumor
In spite of the
previous failure of the mainstream clinical trial for pancreatic cancer research,
more trials were performed for other types of cancer with this vaccine. And the
new boost was given this year with revealing early results of a clinical trial
being conducted at The Cancer Institute of New Jersey.
Previous studies by
scientists at CINJ have shown that injecting a vaccine and other
immunity-producing drugs into a cancer tumor itself — rather than the traditional
site of the skin — can result in a reversal of the traditional immune blockade
and the development of specific immunity to the tumor. This body-wide
tumor-specific immunity has the potential of blocking the growth of the
original tumor as well as eliminating small deposits of tumor that can cause
the cancer to spread. Stemming from this research is a clinical trial that is
the focus of this poster presentation. The study by CINJ investigators further
tests this vaccine strategy, designed to harness the body’s own immune system
to fight cancer.
Researchers are
utilizing two types of PANVAC, containing gene additives that might stimulate a
person’s immune system to recognize and develop an immune response to the
disease.
PANVAC-V, which uses
the same virus as the smallpox vaccine, is a live but weakened vaccinia vaccine
(meaning the virus can still multiply) that is given in the arm.
PANVAC-F (a live
Fowlpox virus that cannot multiply) is injected into the arm and into the tumor
itself. Direct tumor injection takes place through a procedure known as
endoscopic ultrasound, in which a scope is inserted through the mouth and into
the stomach.
During the first
phase of the study, which looked at six participants whose cancer could not be
removed through surgery, patients were evaluated for toxicity, tumor
progression and the presence of tumor markers for pancreatic cancer. Two
patients were removed from the study after two weeks due to rapid disease
progression. Of the remaining four patients, three had received gemcitabine – a
standard treatment for pancreatic cancer – after receiving vaccination
treatment. The other patient was treated with gemcitabine, followed by
capecitabine and radiation, prior to the vaccination regimen and received no
other treatment after.
Of these four
patients, all were shown to have clinically stable disease after 15 months, 13
months, 12 months and nine months respectively. The second part of the trial is
accruing additional participants, who are being given a higher dosage of
PANVAC-F during direct injection of the tumor.
Elizabeth Poplin,
MD, medical oncologist at CINJ and professor of medicine at UMDNJ-Robert Wood
Johnson Medical School, is the lead researcher on the study, which is sponsored
by the National Cancer Institute (NCI). “By utilizing the body’s own defenses
in this way in combination with traditional therapies, we have an opportunity
to better identify more effective treatment and management options for this
disease, which unfortunately only has a five-year, five-percent survival rate,”
said Dr. Poplin.
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