Safety and Preliminary Evidence of Biologic Efficacy of a Mammaglobin-A DNA Vaccine in Patients with Stable Metastatic Breast Cancer

• Published in: Clinical cancer research Vol. 20; no. 23; pp. 5964 - 5975
• Main Authors: Tiriveedhi, Venkataswarup, Tucker, Natalia, Herndon, John, Li, Lijin, Sturmoski, Mark, Ellis, Matthew, Ma, Cynthia, Naughton, Michael, Lockhart, A. Craig, Gao, Feng, Fleming, Timothy, Goedegebuure, Peter, Mohanakumar, Thalachallour, Gillanders, William E.
• Format: Journal Article
• Language: English
• Published: United States 01.12.2014
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Combined Modality Therapy; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte - immunology; Female; Genetic Vectors - genetics; Humans; Interferon-gamma - metabolism; Male; Mammaglobin A - genetics; Mammaglobin A - immunology; Middle Aged; Neoplasm Metastasis; NK Cell Lectin-Like Receptor Subfamily K - metabolism; Treatment Outcome; Tumor Necrosis Factor-alpha - metabolism; Vaccination; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-14-0059

Purpose: Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy. Experimental Design: Patients with breast cancer with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T-cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival (PFS) was described using the Kaplan–Meier product limit estimator. Results: Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 subjects were HLA-A2+, and the CD8 T-cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A–specific CD8 T cells after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P < 0.001), and ELISPOT analysis demonstrated an increase in the number of MAM-A–specific IFNγ-secreting T cells (41 ± 32 vs. 215 ± 67 spm; P < 0.001). Although this study was not powered to evaluate progression-free survival (PFS), preliminary evidence suggests that subjects treated with the MAM-A DNA vaccine had improved PFS compared with subjects who met all eligibility criteria, were enrolled in the trial, but were not vaccinated because of HLA phenotype. Conclusion: The MAM-A DNA vaccine is safe, capable of eliciting MAM-A–specific CD8 T-cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. Clin Cancer Res; 20(23); 5964–75. ©2014 AACR.