MIAMI BEACHSequential Tri-com vaccines against cancers testing
positive for carcinoembryonic antigen (CEA) have produced one clinical response
and no toxicity among 23 patients in a phase I clinical trial.
John L. Marshall, MD, director of Developmental Therapeutics and
Gastrointestinal Oncology, Lombardi Cancer Center, Washington, DC, presented
preliminary results (abstract 798) at Molecular Targets and Cancer
Therapeutics, an international conference cosponsored by the American
Association for Cancer Research (AACR), National Cancer Institute (NCI), and
European Organization for Research and Treatment of Cancer (EORTC).
"We’ve shown so far that it is safethe patients handled it
extremely welland there’s evidence of clinical activity in one patient
with small-cell lung cancer (SCLC) following just two vaccinations," said
Dr. Marshall, associate professor of medicine, Georgetown University School of
Medicine. He described the Tricom vaccine as "arguably one of the most
potent anticancer vaccines available."
As its name suggests, Tricom contains genes for three moleculesB7-1,
ICAM, and LFA-3that have been shown in preclinical testing to enhance
antigen-specific immune response. The vaccine is attached to a live virus that
has been spliced with a CEA gene in order to improve T-cell activation against
the CEA antigen.
The phase I trial was carried out in three phases. In the first phase,
patients received all doses of the vaccine in a vector of recombinant avipox, a
fowlpox virus that infects birds. For the second phase, the first inoculation
was delivered in recombinant vaccinia, a smallpox vaccine, with the avipox
vector reserved for delivery of booster doses. In the third phase, patients
received the sequence of vaccinia and avipox vectors plus granulocyte
macrophage-colony stimulating factor (GM-CSF), another stimulator of immune
"Vaccinia is the smallpox vaccine in essence. It has been genetically
engineered to carry genes for the immune response," Dr. Marshall said. All
of the patients in the preliminary group had been inoculated previously against
smallpox, but the trial’s protocol has recently been amended to include
people who have not previously been exposed to the smallpox virus.
So far, he said, there has been no evidence to suggest that cancer patients
have weakened immune systems that could make them more vulnerable to smallpox.
"Our vaccine trial clearly shows patients can mount a significant immune
response when guided," he said.