正在進行一期臨床試驗的一種新疫苗會導致人體的免疫係統來追蹤一個名為乳腺球蛋白-A（mammaglobin-A）的蛋白質，該蛋白質在乳腺癌組織中高表達，但在健康組織中該蛋白質的作用尚不清楚。
Safety and Preliminary Evidence of Biologic Efficacy of a Mammaglobin-A DNA Vaccine in Patients with Stable Metastatic Breast Cancer
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.
Footnotes
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Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
- Received January 23, 2014.
- Revision received August 18, 2014.
- Accepted August 19, 2014.
- ©2014 American Association for Cancer Research.
http://clincancerres.aacrjournals.org/content/20/23/5964.abstract
