Using Immunotherapy to Fight Cancer
Immunotherapy is a fast growing area of research at Moffitt. Studies include developing therapies that use a patient’s own immune system to fight and destroy cancer. Moffitt researchers, led by physician-scientist Brian J. Czerniecki, M.D., Ph.D., are currently using this approach to create vaccines from immune cells called dendritic cells. These cells are harvested from each individual patient and then used to create a personalized vaccine that directs an attack on the progression of breast cancer by targeting the HER2 protein.
Targeting the HER2 Protein
The vaccine is designed help early-stage breast cancer patients who have HER2 positive disease. The HER2 protein is over expressed in nearly 25 percent of all breast cancer tumors and is associated with aggressive disease and poor prognosis. Moffitt researchers 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.
Breast Cancer Vaccine Findings
In order to determine if the HER2-dendritic cell vaccine is safe and effective, researchers performed a clinical trial that included 54 women who have HER2-expressing early-stage breast cancer.
During the trial, dendritic cell vaccines were prepared by isolating dendritic cells from each patients’ blood and exposing them to fragments of the HER2 protein. Patients were then injected with an activated 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 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 and the response does not appear to affect normal tissue.
The effectiveness of the vaccine was assessed 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. Researchers 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.
The full study, which was published in the Dec. 13 issue of Clinical Cancer Research, can be viewed by clicking here. The study was supported by funds received from the National Cancer Institute (R01-CA096997, P30-CA016520), Pennies-in-Action® and the Henle Foundation.
Targeting HER2 and other Oncodrivers in Invasive Breast Cancer
Besides targeting HER2 in DCIS the researchers are also using anti-oncodriver vaccines to restore lost immune responses in patients with invasive breast cancer having residual disease after neoadjuvant chemotherapy. In addition these approaches are being combined with standard therapies of chemotherapy and radiation as well as other immune stimulating therapies to improve survival and treat patients with more advanced HER2 and triple negative breast cancers. Patients interested in these advanced therapies can be seen and evaluated this summer in the newly formed HER2 multidisciplinary clinic at Moffitt Cancer Center. For more information on these trials, please contact us.
We would be happy to answer any questions providers may have regarding treatments available, open or upcoming trials in the Breast Oncology Program. Please contact Moffitt Physician Relations using the form below.