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 studied 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.
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. 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 full study, which was published in the Dec. 13 issue of Clinical Cancer Research. 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 in the newly formed HER2 Multidisciplinary Clinic at Moffitt Cancer Center.
Moffitt hosts numerous breast cancer trials, offering patients access to some of the latest innovations in treatment before those treatments are approved for use in other settings. Many Breast Program faculty members are principal investigators for phase one and phase two clinical trials evaluating novel breast cancer therapies designed to improve prognosis, reduce side effects and improve quality of life. To learn more about the clinical trials currently available at Moffitt, contact us at 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.
Dr. Czerniecki connected with our Facebook friends in the Ask The Experts series to answer more questions about the breast cancer vaccine.