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

Venkataswarup Tiriveedhi, Natalia Tucker, John Herndon, Jin Li, Mark Sturmoski, Matthew Ellis, Cynthia Ma, Michael Naughton, Albert Lockhart, Feng Gao, Timothy Fleming, Peter Goedegebuure, Thalachallour Mohanakumar, William E. Gillanders

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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.

Original languageEnglish (US)
Pages (from-to)5964-5975
Number of pages12
JournalClinical Cancer Research
Volume20
Issue number23
DOIs
StatePublished - Dec 1 2014
Externally publishedYes

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Mammaglobin A
DNA Vaccines
Breast Neoplasms
Safety
Disease-Free Survival
T-Lymphocytes
Enzyme-Linked Immunospot Assay
Flow Cytometry
Vaccination
HLA-A2 Antigen
Clinical Trials, Phase I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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; Tucker, Natalia; Herndon, John; Li, Jin; Sturmoski, Mark; Ellis, Matthew; Ma, Cynthia; Naughton, Michael; Lockhart, Albert; Gao, Feng; Fleming, Timothy; Goedegebuure, Peter; Mohanakumar, Thalachallour; Gillanders, William E.

In: Clinical Cancer Research, Vol. 20, No. 23, 01.12.2014, p. 5964-5975.

Research output: Contribution to journalArticle

Tiriveedhi, V, Tucker, N, Herndon, J, Li, J, Sturmoski, M, Ellis, M, Ma, C, Naughton, M, Lockhart, A, Gao, F, Fleming, T, Goedegebuure, P, Mohanakumar, T & Gillanders, WE 2014, 'Safety and preliminary evidence of biologic efficacy of a mammaglobin-A DNA vaccine in patients with stable metastatic breast cancer', Clinical Cancer Research, vol. 20, no. 23, pp. 5964-5975. https://doi.org/10.1158/1078-0432.CCR-14-0059
Tiriveedhi, Venkataswarup ; Tucker, Natalia ; Herndon, John ; Li, Jin ; Sturmoski, Mark ; Ellis, Matthew ; Ma, Cynthia ; Naughton, Michael ; Lockhart, Albert ; Gao, Feng ; Fleming, Timothy ; Goedegebuure, Peter ; Mohanakumar, Thalachallour ; Gillanders, William E. / Safety and preliminary evidence of biologic efficacy of a mammaglobin-A DNA vaccine in patients with stable metastatic breast cancer. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 23. pp. 5964-5975.
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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.",
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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, Albert

AU - Gao, Feng

AU - Fleming, Timothy

AU - Goedegebuure, Peter

AU - Mohanakumar, Thalachallour

AU - Gillanders, William E.

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.

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