Preliminary work with a cancer vaccine
derived from heat-shock proteins
(HSPs) taken from the patient's own
tumor has led to impressive early results
in resected pancreatic cancer.
Robert G. Maki, MD, presented the
findings at the European Cancer Conference
(ECCO 12, abstract 48).
Cancer vaccines based on autolo-
gous heat-shock proteins are of interest
because they can carry a diverse
array of peptides representing an individual
cancer against which a patient
can be vaccinated, said Dr. Maki, of
the Division of GI Oncology, Department
of Medicine, Memorial Sloan-
Kettering Cancer Center.
cancer vaccine contains the antigenic
fingerprint of the patient's particular
cancer, and is designed to direct the
body's immune system to target and
destroy only cancer cells bearing that
specific antigenic fingerprint," he said.
The phase I study included 10 evaluable
patients with resected pancreatic
adenocarcinoma given an autologous
vaccine (heat-shock protein
peptide complex-96). Although the
average survival after surgery for pancreatic
cancer is 14 to 15 months, patients
in this trial had a median survival
of 2.5 years, Dr. Maki reported.
One patient was still alive and without
disease after 5 years, and two other
patients were alive and disease-free
after more than 2 years following treat-
ment. There was no significant observed
toxicity associated with the vaccine
The trial enrolled patients who had
undergone pancreatic resection and
were considered disease-free at vaccination.
None had received chemotherapy
or radiation therapy. Within
8 weeks of surgery, they began treatment:
one vaccination of 5 μg HSPPC-
96 derived from their own tumor
each week for 4 weeks.
During vaccination, patients were
followed by ELISpot assay of autologous
T cells against antigen-presenting
cells loaded with autologous HSPPC-
96. After the vaccination, patients
were followed clinically by CT scan
and CA-19-9 every 3 months for 1 year
for evidence of recurrence and about
every 6 months thereafter.
"What is notable is the duration of
the survival observed in this study,
since more than 90% of patents with
pancreatic cancer die within 2 years of
diagnosis despite surgical treatment,"
Dr. Maki said. "Combined with the
lack of dose-limiting toxicity observed
in this trial, these preliminary results
are promising and support the further
evaluation of cancer vaccines."
Dr. Maki warned, however, that
physicians and patients should not get
too excited about the results of this
initial research as it is too early to tell
whether it will be possible to create
personalized cancer vaccines for all
pancreatic cancer patients, and also
because the patients involved in this
trial had been carefully selected.
"We may be biased in who we selected
for this study. Only patients
who could have an operation were
eligible. Furthermore, we screened out
those who had evidence of tumor
spread before they entered the study.
Perhaps, just by chance, we got a few
people who were destined to do well,"
Dr. Maki said. "We need a proper
randomized study to determine the
He pointed out that there were initial
problems with the vaccine's manufacturing
process, and the study was
delayed half way through to improve
the vaccine-making process. "The
problem is that the pancreas makes
specific digestive enzymes that destroy
proteins," Dr. Maki said. "In other
words, the pancreatic tumor cells
themselves can destroy the vaccines
you are trying to make if you do not
handle the tumor tissue carefully and
quickly." With improvements in the
vaccine-purification process, he said,
most patients enrolled in the study
were able to receive the vaccine.
The results from the phase I pancreatic
cancer trial are "consistent with
what we have observed in trials of this
vaccine with other cancers," Dr. Maki
said. The vaccine is being tested in
phase III trials in renal cell carcinoma
and metastatic melanoma, and is also
being studied in gastric cancer, non-
Hodgkin's lymphoma, and colorectal
New York-based Antigenics Inc.,
the company sponsoring these trials,
has been granted fast track and orphan
drug designations from the FDA
for HSPPC-96 (Oncophage) in both
metastatic melanoma and renal cell