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

1. Venkataswarup Tiriveedhi1,2,
2. Natalia Tucker1,
3. John Herndon1,
4. Lijin Li1,
5. Mark Sturmoski1,
6. Matthew Ellis3,4,
7. Cynthia Ma3,4,
8. Michael Naughton3,4,
9. A. Craig Lockhart3,4,
10. Feng Gao4,5,
11. Timothy Fleming1,4,
12. Peter Goedegebuure1,4,
13. Thalachallour Mohanakumar1,4,6, and
14. William E. Gillanders1,4,*

+ Author Affiliations

1. ¹Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
2. ²Department of Biological Sciences, Tennessee State University, Nashville, Tennessee.
3. ³Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
4. ⁴The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
5. ⁵Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
6. ⁶Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.

1. ↵*Corresponding Author:
   William E. Gillanders, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, PO Box 8109, Saint Louis, MO 63110. Phone: 314-747-0072; Fax: 1-314-454-5509; E-mail: gillandersw@wustl.edu

Abstract

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.