MIAMI BEACH—Sequential 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 safe—the patients handled it extremely well—and 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 molecules—B7-1, ICAM, and LFA-3—that 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 response.
"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.
