Recombinant Vaccines Under Development

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 annual session.

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 NCI’s 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 for immunotherapy.

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. "I’m 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 system."