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Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

ABSTRACT: 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.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.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 IFN?-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.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.

SUBMITTER: Tiriveedhi V

PROVIDER: S-EPMC4322416 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

Tiriveedhi Venkataswarup V Tucker Natalia N Herndon John J Li Lijin L Sturmoski Mark M Ellis Matthew M Ma Cynthia C Naughton Michael M Lockhart A Craig AC Gao Feng F Fleming Timothy T Goedegebuure Peter P Mohanakumar Thalachallour T Gillanders William E WE

Clinical cancer research : an official journal of the American Association for Cancer Research 20141201 23

<h4>Purpose</h4>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.<h4>Experimental design</h4>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 (P ...[more]

PMID: 25451106

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Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

Publications

Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer.

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