SAN FRANCISCOA new approach to stimulating the immune system
against a cancer antigen has produced a clinical response in a small number of
colorectal cancer patients enrolled in a phase I/II trial, according to a
poster presented at the 37th Annual Meeting of the American Society of Clinical
Lawrence Fong, MD, of Stanford University Medical Center,
reported that researchers were able to increase dendritic cells as much as
20-fold within the patient, remove the dendritic cells from the patient’s
blood and load them with an epitope derived from carcinoembryonic antigen (CEA),
then deliver them back to the patient in a vaccine.
The vaccine led to dramatic tumor regression in two patients
with advanced colorectal cancer. One had been cancer free for almost a year at
the time of the presentation, and the other had a recurrence at 10 months. Two
other colorectal patients had stable disease after treatment, and another had a
mixed response, Dr. Fong said. No effect was seen in two lung cancer patients
in the 12-person study.
"It’s feasible, safe, and appears to do what we had
hoped," Dr. Fong told ONI. He expressed optimism that tumor immunology is
moving forward after years of frustrated efforts. "We can actually prime
an immune response," he said. "We can teach the immune system the
things we want to teach it."
Since dendritic cells are rare in the blood, the first step in
the process was to give the patients Flt3 ligand, a hematopoietic growth factor
that fosters growth of dendritic cells.
"We present this as a new way of generating dendritic
cells for vaccines, which is completely contrary to what everybody else is
doing and, if anything, is a little simpler," Dr. Fong said. He said that
researchers usually grow dendritic cells outside the patient’s body in a
After 10 days, the dendritic cells were removed from the
patients’ blood and loaded with the epitope, which is similar to CEA. The
researchers then returned the cells to the patients in a vaccine.
Tricking the Immune System
The goal, Dr. Fong said, was to trick the immune system into
attacking CEA. "T cells see CEA as something that is normally in our
bodies, and they wouldn’t typically attack it. So in order to turn on the T
cells, we immunize with something that is just a little different from CEA,"
he said. Once the modified epitope triggers an immune response, the immune
system can target CEA because it is so similar to the epitope.
CEA is overexpressed in more than 90% of colorectal cancers,
70% of non-small-cell lung cancers, and about 50% of breast cancers, Dr. Fong
said. Consequently, a vaccine that targets CEA could be applicable to some of
the top cancer killers in the United States. He described the phase I/II
results as "ground to stand on" for additional work.
Dr. Fong cautioned that developing a cancer vaccine for FDA
approval will take years of research. He also predicted, however, that the
process may be speeded up by new tools that can reveal how minor adjustments in
experimental vaccines affect the immune system. For example, his group used a
tetramer test developed at Stanford to correlate clinical responses with in
vivo changes caused by the epitope vaccine.
"Now, hopefully, we can continue to make consistent
incremental progress because we have better tools for understanding what we are
doing," he said.