SAN DIEGO--Researchers are becoming more optimistic about the
possible benefits of recombinant vaccines in fighting carcinomas,
Jeffrey Schlom, PhD, said at the American College of Physicians
The potential targets for these vaccines are either tumor-associated
or tumor-specific gene products, which are commonly found in many
cancers. Dr. Schlom, chief of the NCIs Laboratory of Tumor
Immunology and Biology, said that one of the most studied tumor
markers is CEA, which is overexpressed in most colorectal, gastric,
pancreatic, and mammary tissue. Scientists have focused on
constructing a recombinant CEA vaccinia virus (rV-CEA) as a vaccine
Phase I clinical trials employing rV-CEA in patients with metastatic
cancers were designed to determine whether CEA is immunogenic in
humans. Researchers found that the answer was "overwhelmingly
yes," he said. "There was no toxicity and some induction of
immune response." He also indicated that several cytokines, such
as IL-2 and GM-CSF, have now been shown to enhance vaccine efficacy.
Dr. Schlom is involved in phase II trials of several different
vaccine strategies that are just beginning at Georgetown University,
Dana-Farber Cancer Institute, Duke University, and the National
Cancer Institute. These trials, which will include patients with
breast, colorectal, prostate, and lung cancers, involve cytokines,
T-cell costimulatory molecules, diversified prime and boost
schedules, and, perhaps 1 year down the road, agonist peptides.
"These new developments can also be exploited toward the
development of recombinant vaccines for a range of infectious
diseases, including HIV," he added.
Any Clinical Remissions?
When asked if recombinant vaccines are producing any clinical
remissions, Dr. Schlom said that in phase I trials, researchers saw a
drop in tumor markers. But, he pointed out, these were patients with
advanced cancer unlikely to have disease remission. Since the
patients in the phase II trials are only weeks into the study, it is
too early to tell if clinical remissions will occur.
He was also asked if recombinant vaccines would work in patients who
have undergone multiple rounds of chemotherapy. "Im amazed
that we are seeing immune responses in these patients," Dr.
Schlom said. "But the place for these vaccines is in an adjuvant
setting, after surgery, while the patient still has a strong immune