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News Archive - Progress Newsletter Summer 2001 Online
Dendritic cell vaccine shows promise against pediatric cancer
Results from the first-ever study testing the use of dendritic cells in children may offer new hope for a cancer vaccine.
The phase I study's findings suggest that dendritic cells spiked with cancer proteins from a pediatric patient's own tumor can generate an immune response to the cancer, and may spark stabilization or regression of metastatic, or spreading, cancers. One of the 13 study participants, a 16-year-old with cancer that had spread to her lungs and spine, showed significant tumor regression. Five others saw their disease stabilize."
"We've shown that dendritic cell vaccines seem to have the best potential of all other cancer vaccines we've looked at so far to change the immune response to tumors," says James D. Geiger, M.D., assistant professor of surgery and the study's principal investigator. "This study is certainly not a home run, but it does give us a lot of encouragement."
Dr. Geiger calls dendritic cells the "quarterbacks" of the immune system. They are specialized white blood cells whose job it is to alert the immune system to the presence of invading cancers, bacteria or viruses so the invaders can be surrounded and destroyed.
In the study performed at the U-M Comprehensive Cancer Center, blood was drawn from each of 13 children, ages 3 to 17. All of the children had end-stage cancer - relapsed solid malignancies that had failed to be successfully treated with standard therapies. Among the 13 children, a variety of pediatric tumor types were treated including three neuroblastomas, four sarcomas, one osteosarcoma, one fibrosarcoma, two undifferentiated sarcomas, one renal sarcoma and one Wilms' tumor.
From each patient's blood, the U-M team isolated dendritic cells, enticed them to replicate, then sensitized them to the tumor before injecting them back into the patient.
Earlier, U-M basic research by James J. Mulé, Ph.D., Maude T. Lane Professor of Surgical Immunology and director of the U-M Tumor Immunotherapy Program, revealed that when dendritic cells find cancer cells, they sound the alarm to the rest of the immune system by displaying pieces of digested tumor proteins called antigens on long projections.
The dendritic cell presents these antigens to other white blood cells called T-lymphocytes until it finds those lymphocytes with receptors that fit the tumor antigen. Once a match is made, T-lymphocyte "clones" - all equipped with the exact receptor needed to attack and destroy one specific type of tumor cell - attack the cancer cells.
"All vaccines were delivered in an outpatient setting with no obvious toxicity," Dr. Geiger says.
In the next phase of the trial, Dr. Geiger says he and his fellow researchers hope to find ways to improve the vaccine, employing methods to augment it and using it to treat patients with minimal disease who have finished more standard treatments.
"This would allow us to have a better chance to impact the health of the patients," Dr. Geiger says. "Immunotherapies are likely most effective when they are used early or when used after a standard treatment, when there's only microscopic disease present."
This work was supported by grants from the National Institutes of Health's National Cancer Institute and the University of Michigan Health System General Clinical Research Center.
Cancer Center researchers have found a molecular link between aggressive breast and lymphatic cancers and the Epstein-Barr virus, which causes infectious mononucleosis.
In a paper published in the March 2001 issue of Nature Medicine, scientists show how the Epstein-Barr virus alters the function of a cellular protein that normally suppresses the movement of malignant cells. When this natural brake on cell migration is disabled by the virus, cancerous breast and lymphatic cells are free to metastasize or spread.
"This is the first evidence of a human virus associated with the development of cancerous tumors targeting a cellular protein to promote the migration of malignant cells," says Erle S. Robertson, Ph.D., who directed the study. Robertson is an assistant professor of microbiology and immunology in the U-M Medical School.
"The Epstein-Barr virus is associated with many human cancers - including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease and invasive breast cancer," Dr. Robertson says.
The virus is very common. More than 90 percent of adults show signs of previous viral infection. Adolescents infected with the acute phase of the virus can develop infectious mononucleosis, but usually the body's natural immune response forces the virus to revert to its latent phase - where it hides inside the nucleus of immune cells called lymphocytes without producing any symptoms.
Even though the virus is endemic in humans, Robertson emphasizes that most cells infected by the virus may never become malignant. Additional genetic factors are required to trigger development of cancer. Should cancer develop, however, Robertson says the risk of metastasis may be higher in individuals previously exposed to the virus.
"People with aggressive forms of cancer are most vulnerable and should be checked to determine the status of previous viral exposure when physicians are choosing the most appropriate treatment for them," Robertson says. "It also would be wise to closely monitor people with a history of active Epstein-Barr viral infection for early signs of cancer."