Renal Cancer Vaccine Builds Upon Promise of Dendritic Cell Technology
DURHAM, N.C. -- A new Phase I clinical trial shows that a renal cancer vaccine developed at Duke University Medical Center is safe and effective in boosting cancer patients' immune systems. None of the 10 patients in the study suffered adverse side effects from the vaccine.
The results of the trial are published in the May 1, 2003, issue of Cancer Research.
"In a previous study, we showed that a prostate cancer vaccine using dendritic cells was not only safe, but also that it triggered a immune response in patients," said Johannes Vieweg, M.D., an associate professor of urology and assistant professor of immunology at Duke University Medical Center and senior investigator in the study. "This study builds upon that research, showing the technology to be flexible enough to use in a variety of different cancers."
Dendritic cells are white blood cells that activate the immune system by capturing antigens -- substances that trigger an immune response, such as against viruses, bacteria, or tumors -- and presenting them to the body's killer cells called T cells to activate those cells. The vaccine used in the Duke study consists of cultured dendritic cells into which genetic information has been introduced in the form of RNA from a renal cancer patient's own tumor. The dendritic cells use the RNA to produce and display antigens to the tumors on their surface. So, when the altered dendritic cells are injected back under the patient's skin, they activate the patient's own T-cells to attack the tumors.
"In our previous trial, the vaccine was directed against one specific antigen," said Vieweg. "In this trial, we see that the vaccine can target multiple antigens successfully, without attacking antigens expressed by normal renal tissues."
In the trial, 10 patients with late-stage metastatic renal cancer were given three escalating doses of the vaccine. The vaccine was well tolerated, and none of the participants exhibited any significant side effects. "By using cells from the patient's own body, we are able to create a vaccine that causes very few, if any, adverse events," said Vieweg.
Metastatic renal cancer is extremely deadly. Most patients have approximately nine to 12 months to live after diagnosis. One of the most encouraging results from the study is that out of 10 patients only three died in the 19.8 months of follow up. Vieweg sees the increased survival rate as promising, but cautions that the patients had additional treatments during the trial, so additional studies are needed to confirm the clinical implications.
"We frequently saw a stabilization of the disease in patients," said Vieweg. "This is encouraging because it shows that while we may not be able to kill tumors completely at this point, we can slow or stop the disease from progressing. The vaccine has no toxicity and causes no serious side effects. So if we can give these patients a longer life span, but also better quality of life during that time, then we would consider that treatment a success."
The researchers performed immunological tests to ensure that T cells were functioning and able to kill tumor cells, and also tested to determine whether the number of T cells rose. In six out of seven subjects able to be evaluated, tumor-specific T-cells increased after immunization, suggesting the vaccine was successful in boosting the immune system and turning T cell attention to the cancer.
Vieweg said that the immunological data, which is sometimes not collected, is highly important in proving that the cancer vaccine is working in the patient and other influences are not responsible for the changes.
"If a trial only studies a reduction in tumor growth, there is a large part of the story that goes untold," Vieweg said. "There are subclinical changes that occur in the body that indicate if a vaccine is promising. Without the immunological studies, which are time consuming and complex, we cannot confirm the cause and effect relationship that the vaccine has on the growth of T cells and immune system."
Such data are a vital part of our systematic approach to developing these vaccines and validating each step of the sequence."
Vieweg says that the next step is use a more potent or "mature" dendritic platform and to study the immune and clinical responses to such robust vaccines. His team will also be examining the overall durability and sustainability of the vaccines.
The study was supported by grants from the National Institutes of Health and the National Center for Research Resources.
Other authors of this study include: Zhen Su, Ph.D.; Jens Dannull, M.D.; Axel Heiser, Ph.D.; Donna Yancey; Scott Pruitt, M.D., Ph.D.; John Madden, M.D.; Doris Coleman; Donna Niedzwiecki, Ph.D.; and Eli Gilboa, Ph.D., all of Duke University Medical Center.