Phase 1B Clinical Trial of a Candidate Breast Cancer Prevention Vaccine
Abstract
Which overarching challenge(s) does this research address? The research proposed in this application addresses two overarching challenges: (1) revolutionize treatment regimens by replacing interventions that have life-threatening toxicities with ones that are safe and effective, and (2) prevent breast cancer (primary prevention). What types of patients will it help and how will it help them? We propose a clinical trial testing the efficacy of a breast cancer vaccine targeting mammaglobin-A, a gene that was first identified by Dr. Fleming, a member of our scientific team. In our studies of the biology of mammaglobin-A, we have determined that mammaglobin-A has a number of unique characteristics that make it an ideal target for a breast cancer vaccine. Mammaglobin-A is overexpressed in the majority of breast cancers, and with almost no expression in other tissues. In addition, the immune system appears to be able to recognize mammaglobin-A. If we are able to successfully develop a breast cancer vaccine targeting mammaglobin-A, it could be used as a treatment in most breast cancer patients. Mammaglobin-A is expressed in all subtypes of breast cancer, although it is expressed most commonly in patients with ER-positive breast cancers. What are the potential clinical applications, benefits, and risks? We believe that a mammaglobin-A vaccine could be used either as a treatment for breast cancer or ultimately as part of a prevention vaccine for breast cancer. As a treatment, the mammaglobin-A vaccine is most likely to be effective in the adjuvant setting -- to prevent breast cancer recurrence in women who have been successfully treated with traditional breast cancer treatments (surgery, radiation, chemotherapy) but who are at risk for disease recurrence. Alternatively, as a prevention strategy, the mammaglobin-A vaccine could be used to prevent breast cancer in women who are at high risk of developing breast cancer (family history, history of abnormal biopsy). Mammaglobin-A is expressed in the majority of breast cancers. As such, a mammaglobin-A breast cancer vaccine has the potential to prevent recurrence in most breast cancer patients if used as a treatment vaccine and has the potential to prevent most breast cancers if used as a prevention vaccine. We recently completed a Phase 1 clinical trial of the mammaglobin-A vaccine. The vaccine was shown to be safe with minimal side effects. The excellent safety profile of cancer vaccines, including DNA vaccines, is one of the reasons why we are so excited to pursue the clinical development of the mammaglobin-A DNA vaccine. What is the projected time it may take to achieve a patient-related outcome? We have completed a Phase 1 clinical trial in breast cancer patients with metastatic disease. This first-in-human clinical trial was a success as the vaccine was safe with minimal side effects and was capable of generating a productive immune response, with preliminary evidence of an improved progression-free survival. Thus, the mammaglobin-A vaccine appears to have already made a patient-related outcome. We now propose a Phase 1b trial to integrate a new technology (electroporation) and an innovative clinical trial design. We will vaccinate patients who are being treated with neoadjuvant endocrine therapy. This will allow us to obtain tissue specimens from breast cancer patients both before and after vaccination. Specimen acquisition will be integrated into routine care, so no additional biopsies will be required. This innovative clinical trial design will allow us to determine if the immune response generated following vaccination has an impact on the primary breast cancer. Studying the immune response in the primary breast cancer is likely to be much more informative than studying the immune response in the blood. Evidence of a robust immune response in the primary breast cancer will help us generate the interest required to move the vaccine into a Phase 3 cl
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510101
Entities
People
- William Gillanders
Organizations
- United States Army
- Washington University in St. Louis