DNA Vaccine Targeting Mammaglobin-A Produces Robust Immune Response in Metastatic Breast Cancer
In a phase I study, a DNA vaccine targeting the breast cancer–associated antigen mammaglobin-A (MAM-A) was found to be safe and effective in eliciting immune responses in women with metastatic breast cancer. Preliminary evidence also suggests that the vaccine improved progression-free survival in the women treated with the vaccine. Additional studies are needed to define the clinical potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. The study by Tiriveedhi et al is published in Clinical Cancer Research.
Study Methodology
Study investigators initiated a phase I clinical trial of a novel MAM-A DNA vaccine in patients with breast cancer with stable metastatic disease. The primary objective of the study was to evaluate the safety of the MAM-A DNA vaccine. Secondary and exploratory objectives included measuring the CD8 T-cell response to the vaccine and the impact on progression-free survival.
Men or women 18 years or older with metastatic breast cancer that had been stable for at least 30 days after their last dose of therapy were eligible for enrollment. A total of 53 participants were enrolled in the study between 2009 and 2013. Following enrollment the HLA phenotypes of the participants were determined and breast cancer specimens were evaluated for MAM-A protein expression.
Fourteen participants met all eligibility criteria and were vaccinated.
Study Results
The researchers found that the vaccine was safe and produced no significant adverse events in the patients. Using flow cytometry, the researchers measured the frequency of mammaglobin-A–specific CD8 T cells at baseline and after vaccination, and found that it increased more than fourfold, indicating a robust immune response. And while the study was not powered to evaluate progression-free survival, preliminary evidence suggests that the participants treated with the MAM-A DNA vaccine had improved progression-free survival compared with the participants who met all eligibility criteria, were enrolled in the trial, but were not vaccinated because of HLA phenotype.
“I predict that this vaccine and similar vaccines could have the greatest clinical impact in patients who have completed standard treatment regimens, such as chemotherapy, surgery, or radiation, to minimize the risk of recurrence,” said William E. Gillanders, MD, Professor of Surgery at Washington University School of Medicine in St. Louis, and corresponding author of the study, in a statement. “That would help to improve the overall success rate associated with current treatment paradigms.”
“Studies to define the clinical potential of a MAM-A DNA vaccine are particularly important given the safety of the vaccine, evidence of biologic efficacy, exquisite tissue specificity, and near-universal expression of MAM-A in breast cancer, and the potential of MAM-A as a target for a breast cancer prevention vaccine,” concluded the researchers.
The study was funded by the U.S. Department of Defense, Gateway for Cancer Research, the Foundation for Barnes-Jewish Hospital, and the National Cancer Institute.
Timothy Fleming, PhD, holds a patent on mammaglobin that is owned by Washington University. The other study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
