Overriding Systemic and Local Immunologic Checkpoints to Maximize Breast Cancer Immunotherapy
Posted October 25, 2012
Leisha Emens M.D., Ph.D., Johns Hopkins Kimmel Cancer Center
Cancer vaccines present a valuable therapeutic option with the potential for reduced treatment side effects and long-lasting protection against disease. Dr. Leisha Emens, a Fiscal Year 2006 Clinical Translational Research (CTR) Award recipient, has been working to develop a therapeutic breast cancer vaccine for use in combination with standard cancer therapies to enhance efficacy of these treatments. Preclinical studies in mice showed that treatment with granulocyte/macrophage colony-stimulating factor - secreting breast cancer vaccine in combination with chemotherapeutic agent cyclophosphamide (CY) and trastuzumab, a HER-2/neu-specific monoclonal antibody, prevented the outgrowth of established tumors in about 55% of HER2/neu mice tested.
These and other promising preclinical results provided the necessary evidence to move this immunotherapeutic agent into a clinical trial that tested vaccine-CY-trastuzumab combination therapy in 20 women with stage IV metastatic HER2+ breast cancer. Study measures included safety of the treatment and clinical benefit, defined as including complete or partial response to treatment (tumor shrinkage) or stabilization of disease (halted growth or spread). At 6 months, clinical benefit was observed at 50% and at one year clinical benefit was present at 35%. Furthermore, seven of the twenty patients developed new or increased immunity via delayed type hypersensitivity, a cell-mediated immunotherapeutic response. Early exploratory analysis of study results showed that overall survival was 40 months, a significant improvement over the historical overall survival of 12 to 24 months for similar patients who received trastuzumab treatment alone. Furthermore, the safety profile developed from this study indicates that this treatment regimen has minimal harmful side effects and does not impair quality of life.
Results achieved under her FY06 CTR Award have aided Dr. Emens in obtaining additional funding to continue clinical trial work on this vaccine in a larger breast cancer study as well as enabling her to expand study of similar immune-based strategies in other gynecological malignancies. While improving patient outcomes when integrated with traditional drug therapies, cancer vaccines like this one may also have the potential to treat tumors that have developed resistance to standard cancer therapies-a crucial, unmet need in breast cancer.Links: