Jefferson scientists encouraged by trial results of next-generation vaccine for melanoma
A vaccine for advanced melanoma created from a patient's own tumor cells has shown some early signs of causing immune responses in recipients. The vaccine is a second-generation version that aims to improve on the earlier successes of a vaccine created by David Berd, M.D., professor of medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at Jefferson's Kimmel Cancer Center.
While it's still in the initial stages of testing, Dr. Berd and his co-workers are encouraged by the first results and hopeful they bode well for the vaccine's future use. Dr. Berd presents his team's results June 7 at the annual meeting of the American Society of Clinical Oncology in New Orleans.
In earlier work, Dr. Berd and his colleagues found that 44 percent of patients with malignant melanoma – a potentially deadly skin cancer that has spread elsewhere in the body – who were enrolled in a Phase II clinical trial and who received the original vaccine following standard surgery for stage III disease lived at least five years. Only about 20 percent live that long with surgery alone. The original vaccine consisted of tumor cells modified with one chemical. In the current trial – which is a phase I-II study – the scientists are focusing on safety and indications of patients' immunological responses.
Dr. Berd and his co-workers looked at 23 patients with advanced melanoma. Each patient received a vaccine prepared from his or her own cancer cells. The cells are inactivated and modified with two chemicals called haptens – dinitrophenyl (DNP) and sulfanilic acid – which are believed to 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. A stronger DTH indicates an aroused immune system.
At the highest dose, 8 of 10 patients developed positive responses to their own tumor cells that were chemically modified, and 6 of 10 had responses to their unmodified cells. Dr. Berd believes that the latter response is particularly important because it may reflect an immune response against the tumor occurring in the body.
"There is some evidence that this is occurring, since four patients have shown evidence of inflammation in their tumors as determined by physical examination and biopsy," he says. "We think that the development of inflammation in tumors is a sign that the vaccine is inducing the infiltration of white blood cells into the tumor," Dr. Berd says. "In one case so far a metastatic tumor has decreased in size by greater than 50 percent." They are testing patients at one of three doses of vaccine. Each dose has a ten-fold difference in strength.
"Immunochemically, it's different," he says, speaking about the new vaccine. "The two haptens modify different amino acids. Theoretically, having tumor antigens modified by two different haptens should make the tumor more immunogenic."
With the new vaccine, all the required doses are manufactured at once, rather than one at a time prior to injection, and are frozen. "This is a technical improvement that may eventually enhance the potential of this new vaccine for commercialization if it is proven effective," he notes. According to Dr. Berd, his team is continuing to analyze data from the initial group of patients, and he hopes later this year to begin enrolling more.
Dr. Berd says that a Phase II study may be possible next. The researchers may also explore the possibility of developing a similar vaccine against another type of cancer, possibly ovarian.
The research was supported by the National Institutes of Health and by AVAX Technologies, Inc., of Kansas City, MO, which has exclusive rights to the original Jefferson-based vaccine against malignant melanoma.
More than 40,000 new cases and 7,000 deaths will occur this year from the melanoma, the fifth most common cancer in the nation.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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