Dendritic Cell Vaccine Effective in Early-stage Breast Cancer
Immunotherapy is a fast growing area of cancer research. It involves developing therapies that use a patient’s own immune system to fight and kill cancer. Moffitt Cancer Center is working on a new vaccine that would help early-stage breast cancer patients who have HER2 positive disease.
The HER2 protein is overexpressed in nearly 25 percent of all breast cancer tumors and is associated with aggressive disease and poor prognosis. Moffitt researchers, led by physician-scientist Brian J. Czerniecki, M.D., Ph.D., have previously shown that immune cells are less able to recognize and target cancer cells that express HER2 as breast cancer progresses into a more advanced and invasive stage. This suggests that strategies that can restimulate the immune system to recognize and target HER2 early during cancer development may be effective treatment options.
The researcher team developed a vaccine that helps the immune system recognize the HER2 protein on breast cancer cells. Their approach involves creating the vaccine from immune cells called dendritic cells that are harvested from each individual patient and then used to create a personalized vaccine.
In order to determine if the HER2-dendritic cell vaccine is safe and effective, the Moffitt researchers performed a clinical trial that included 54 women who have HER2-expressing early-stage breast cancer. The dendritic cell vaccines were prepared by isolating dendritic cells from each patients’ blood and exposing them to fragments of the HER2 protein. Patients were injected with a dose of their personal dendritic cell vaccine once a week for 6 weeks into either a lymph node, the breast tumor, or into both sites.
The study, which was published in the Dec. 13 issue of Clinical Cancer Research, showed that the dendritic cell vaccine was well-tolerated and patients only experienced low-grade toxicities. The most common adverse events were fatigue, injection site reactions, and chills. The results also showed the vaccine was able to stimulate an immune response in the majority of the patients. Approximately 80 percent of trial participants had a detectable immune response in their peripheral blood and/or in their sentinel lymph node wherein their cancer is most likely to spread to first. Importantly, the immune responses among the patients were similar, regardless of the route of vaccine administration.
Moffitt researchers assessed the effectiveness of the vaccine by determining the percentage of patients who had detectable disease within surgical specimens after resection. The absence of disease is termed a pathological complete response. They report that 13 patients achieved a pathological complete response and patients who had early non-invasive disease called ductal carcinoma in situ (DCIS) achieved a higher rate of pathological complete response than patients who had early-stage invasive disease. Additionally, patients who achieved a pathological complete response had a higher immune response within their local sentinel lymph nodes.
“These results suggest that vaccines are more effective in DCIS, thereby warranting further evaluation in DCIS or other minimal disease settings, and the local regional sentinel lymph node may serve as a more meaningful immunologic endpoint,” said Czerniecki, chair of the Department of Breast Oncology at Moffitt.
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L. Lowenfeld, R. Mick, J. Datta, S. Xu, E. Fitzpatrick, C. S. Fisher, K. R. Fox, A. DeMichele, P. Zhang, S. Weinstein, R. E. Roses, B. J. Czerniecki. Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial. Clinical Cancer Research, 2016; DOI: 10.1158/1078-0432.CCR-16-1924