title: Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. Department of Biological Sciences, Tennessee State University, Nashville, Tennessee.
authors.forename: Venkataswarup
authors.initials: V
authors.lastname: Tiriveedhi
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tucker
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: John
authors.initials: J
authors.lastname: Herndon
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lijin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Mark
authors.initials: M
authors.lastname: Sturmoski
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael
authors.initials: M
authors.lastname: Naughton
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: A Craig
authors.initials: AC
authors.lastname: Lockhart
authors.affiliation: The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri. Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Timothy
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Peter
authors.initials: P
authors.lastname: Goedegebuure
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri. The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri. gillandersw@wustl.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Gillanders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001943:Breast Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D060785:Mammaglobin A / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
chemical_list: D015415:Biomarkers; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C527085:KLRK1 protein, human; D060785:Mammaglobin A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D007371:Interferon-gamma