Jefferson researchers find immune response, dosing keys to vaccine's success against melanoma
How well a patient's immune system reacts to his own cancer cells and the schedule by which the vaccine is given are two key factors in the success of a custom-made vaccine created from the cancer cells of patients with malignant melanoma, the deadliest form of skin cancer and fastest growing cancer in the United States.
Nearly one-half – 44 percent – of malignant melanoma patients enrolled in a clinical trial who received the vaccine following standard surgery lived at least five years – no small achievement, considering that only about 20 percent live that long with surgery alone, according to David Berd, M.D., professor of medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia and Jefferson's Kimmel Cancer Center.
"Although additional, controlled trials will be necessary to prove efficacy, these numbers look promising," says Dr. Berd, who created the vaccine. "We're emphasizing what we call the immunopharmacology of our cancer vaccine, meaning that how the vaccine is administered and the immune response that it elicits strongly influence whether or not a patient will survive five years."
He and his colleagues report their findings in the current issue of the Journal of Clinical Oncology. An editorial accompanies the paper. The phase II trial examined the immunological and clinical results of a vaccine given to 214 melanoma patients with clinical stage III disease, meaning it had spread to lymph nodes that were large enough to be felt by routine examination.
The vaccine was prepared from each patient's own cancer cells. Before injecting the cells into patients, they were inactivated and modified with a chemical, dinitrophenyl (DNP). It is believed that the chemically-altered cells make the cancer cells more visible to the body's immune system, which recognizes and reacts against them.
According to Dr. Berd, the immune response against the cancer cells is measured by a test called delayed-type hypersensitivity (DTH), which is similar to a tuberculosis or allergy test. Patients who developed stronger DTH – indicating an aroused immune system – to their own tumor cells after receiving the vaccine lived twice as long as those who did not.
The way the vaccine was administered mattered to patients as well. The vaccine was given in four different dosing schedules, but the researchers discovered that a particular dosing schedule elicited the maximum immunological response. His group found that if a certain "induction dose" was not given properly, patients had a much weaker immune response to the vaccine.
"In that regard, vaccines are like drugs," he says. "The dose and timing have to be just right."
The immunological response to the tumor cell was important not only in determining if the melanoma grew back, but also affected the length of their survival after relapse. In fact, about 25 percent of the DTH (+) patients who relapsed were still alive after five years.
"That observation suggests that the vaccine changed the biology of the disease," says Dr. Berd. He believes that these findings should be applicable to other experimental cancer vaccines.
"Generally, in the vaccine field, people don't worry about the dose, how often they give it and the injection site," he says. "We show that these things matter. These parameters are important and people will need to figure them out if they want to get their vaccines to work."
Dr. Berd and his colleagues are now developing a second-generation vaccine. The new vaccine involves using an additional chemical to modify tumor cells, making them in theory even more visible to the immune system.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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