TY - JOUR
T1 - Safety and preliminary evidence of biologic efficacy of a mammaglobin-A DNA vaccine in patients with stable metastatic breast cancer
AU - Tiriveedhi, Venkataswarup
AU - Tucker, Natalia
AU - Herndon, John
AU - Li, Jin
AU - Sturmoski, Mark
AU - Ellis, Matthew
AU - Ma, Cynthia
AU - Naughton, Michael
AU - Lockhart, A. Craig
AU - Gao, Feng
AU - Fleming, Timothy
AU - Goedegebuure, Peter
AU - Mohanakumar, Thalachallour
AU - Gillanders, William E.
N1 - Publisher Copyright:
©2014 AACR.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84918783221&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-14-0059
DO - 10.1158/1078-0432.CCR-14-0059
M3 - Article
C2 - 25451106
AN - SCOPUS:84918783221
SN - 1078-0432
VL - 20
SP - 5964
EP - 5975
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -