Vaccine Triggers Colorectal Cancer Patient's Immune System

British investigators have designed a vaccine that triggers colorectal cancer patients' immune systems to destroy cancerous cells.

In a clinical trial of 67 patients, researchers at the University of Nottingham (UK) noted that when the vaccines were given before and after surgery to remove cancerous tumors, they helped stimulate immune cell production in up to 70% of patients. The findings were published in the November 15, 2006, issue of the journal Clinical Cancer Research.

"This is the first vaccine shown to stimulate TNF-alpha--an immune-system protein that is very effective at killing cancer cells,” said Dr. Lindy Durrant, senior investigator of the study and professor of cancer immunotherapy at the university.

The vaccine functions by triggering the patients' immune response to produce infection-fighting white blood cells called T cells, which then generate immune system proteins called cytokines that kill cancer cells. The antibody contained in the vaccine, called 105AD7, was cloned from a patient who survived seven years with liver metastases from colorectal cancer, according to Dr. Durrant.

"This is very unusual as most patients die within one year of getting liver metastases,” she said. "I thought if this antibody had helped this patient, if we could clone it, it might help others.” 105AD7 is structurally similar to CD55, a protein that attaches to glucose molecules and is overexpressed in colorectal cancer cells, protecting them from attack by the body's immune system. Whereas low levels of CD55 occur in all cells exposed to the immune system, increased expression of the protein has been observed in many types of tumors, including up to 80% of colorectal cancers.

During the trial--the largest to date evaluating 105AD7 combined with surgery--67 patients with colorectal cancer who were scheduled for surgery to remove their primary tumor were randomly assigned to receive either 100 micrograms of 105AD7 with a powder to help absorb the vaccine, 105AD7 combined with bacille Calmette Guérin (BCG; a bacteria used to stimulate the immune system in cancer patients), during the first immunization and the powder in subsequent vaccinations, or no treatment.

The patients, who had differing levels of disease, had a median age 66. Twenty-eight patients had colon cancer while in 39 patients the primary tumor was located in the rectum. Patients were immunized before surgery on the day they were recruited for the study, and again two weeks later if surgery had not yet been performed. The vaccines were continued three, six, and 12 weeks after surgery, and then at three monthly intervals up to a maximum of 24 months after surgery. Blood samples were collected from the patients during recruitment, at surgery, and at the time of the three-, six-, and 12-week post-operative immunizations. Additional blood samples were acquired one month after each subsequent immunization.

Laboratory tests of the blood samples indicated that a T-cell response against the vaccine was seen in most of the patients. The responses tended to have two peaks: one following the start of the immunization schedule and another several months later, after additional immunizations. Approximately 70% of patients generated both TNF-alpha and GM-CSF--a protein that stimulates white blood cell production--in response to both the vaccine and to CD55.

"The immune responses to both the vaccine and CD55 were measurable, adding support to the use of CD55 as a target in cancer treatment,” Dr. Durrant remarked. Nineteen of the patients died during the follow-up period. Dr. Durrant and colleagues noted, however, that the trial was not designed to evaluate the effect of the vaccines on survival.



Related Links:
University of Nottingham