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Cancer can be difficult to treat because it tricks the immune system into thinking it's not a threat. Researchers at the Columbia University Medical Center at NewYork-Presbyterian Hospital are participating in a study with a new vaccine that they hope will fool the immune system into fighting colorectal cancer.

Unlike traditional vaccines that are designed to prevent disease by preparing the immune system for a possible attack, this innovative therapeutic colorectal cancer vaccine — ALVAC-CEA/B7.1 — is designed to "turn on" the immune system of people who already have the disease but who have not yet been treated. This therapeutic approach differs from the use of other cancer vaccines, which have been used only as last resorts when chemotherapy and other treatments have failed.

"The goal of the study is to determine if the vaccine can activate the body's own immune system to eliminate cancer cells that may not be eliminated with traditional treatment of metastatic colorectal cancer with standard first-line chemotherapy," explains Howard L. Kaufman, MD, vice chairman of surgical oncology at Columbia University Medical Center, associate professor of clinical surgery at Columbia University College of Physicians & Surgeons, and principal investigator of the study. "We will be looking to see if the vaccine, combined with chemotherapy, allows a better outcome for these patients than chemotherapy alone," he adds.

Since cancer cells do not appear very different from normal cells to the immune system, they are largely tolerated rather than destroyed. However, the surfaces of many cancer cells have special proteins or antigens that can serve as potential targets for an immune response. ALVAC-CEA/B7.1, a deactivated strain of the canarypox virus, is of interest to cancer researchers because of the antigens it displays, which are identical to the antigens exhibited by colorectal tumors. This carcinoembryonic antigen (CEA) is found on the surface of about 95 percent of colorectal cancer cells. The body's immune system should normally fight cells displaying these antigens, but many people with colorectal cancer have immune systems that don't recognize these cells as a threat, and therefore, don't fight them. The idea behind the vaccine is to introduce even more of the tumor-associated antigens (TAA) into the body so the immune system becomes "awakened" or "trained" to attack the cancer cells.

ALVAC-CEA is designed to produce a short-lived and self-limiting harmless infection that causes infected cells to temporarily display CEA. In response, the immune system becomes activated and attacks the tumor cells. B7.1 is a special component of the vaccine known as a costimulatory molecule because it strengthens the immune response produced by ALVAC-CEA.

The trial at Columbia University Medical Center is part of a pilot phase II multicenter trial that includes 12 other medical centers, including sites in Washington, DC, Philadelphia, Los Angeles, Chicago, Florida, and Canada. The trial will enroll 90 patients with previously untreated metastatic colorectal cancer. The study also will incorporate traditional first-line combination chemotherapy-Camptosar (irinotecan or CPT-11), 5-fluorouracil (5-FU), and leucovorin-in its treatment strategy. The researchers believe that the vaccine will promote the immune system to eliminate stray cancer cells not destroyed by chemotherapy or surgery. The study is sponsored by Aventis Pasteur Limited of Toronto, Canada.

Patients at each of the participating medical centers will be randomly assigned to one of three treatment groups. Patients in the first group will receive ALVAC-CEA/B7.1 once a week for three weeks before starting chemotherapy, plus one vaccination at the beginning of each chemotherapy cycle (four cycles), for a total of seven vaccinations. Patients in the second group will undergo this same regimen but will also receive a dose of tetanus toxoid during the first week and tetanus and vaccine for three weeks, prior to chemotherapy cycles to determine if this further enhances the immune response.

Patients will be evaluated routinely for local and systemic adverse effects immediately following treatment and at each follow-up visit. Patients in the third group will receive the standard first-line chemotherapy combination regimen alone. Those who achieve a complete or partial response will have the option of receiving the vaccine upon completion of the four cycles of chemotherapy. Immune response and efficacy measures for objective response and response duration also will be assessed at several predesignated points during the treatment period and at the end of the study.

Single-agent use of this investigational vaccine and other ALVAC-based formulations have shown promise in early clinical studies conducted by the National Cancer Institute (NCI) in collaboration with Therion Biologics of Cambridge, Massachusetts. These studies demonstrated both their safety and their lack of overlapping toxicity with chemotherapy agents.

Colorectal cancer is the most common cancer of the gastrointestinal tract and the second leading cause of cancer-related morbidity and mortality. There are over 147,000 new cases and 57,000 deaths annually from this disease in the United States alone. An estimated 70 percent of patients are initially diagnosed with treatable forms of the disease, but 25 percent of these patients will still experience recurrence, which frequently leads to death due to metastatic disease.