| Title |
Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, June 2012
|
| DOI | 10.1007/s10549-012-2110-9 |
| Pubmed ID | |
| Authors |
Venkataswarup Tiriveedhi, Timothy P. Fleming, Peter S. Goedegebuure, Michael Naughton, Cynthia Ma, Craig Lockhart, Feng Gao, William E. Gillanders, T. Mohanakumar |
| Abstract |
Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS(hi) T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (p < 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (p < 0.05). ELISpot analysis of CD4+ICOS(hi) sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine p < 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine p < 0.001). The ratio of CD4+ICOS(hi) T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (p = 0.021) following vaccination. Further, these activated CD4+ICOS(hi) T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS(hi) T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 33% |
| Belgium | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 3% |
| Unknown | 38 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 23% |
| Student > Ph. D. Student | 7 | 18% |
| Researcher | 4 | 10% |
| Student > Doctoral Student | 4 | 10% |
| Student > Postgraduate | 2 | 5% |
| Other | 3 | 8% |
| Unknown | 10 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 26% |
| Agricultural and Biological Sciences | 9 | 23% |
| Biochemistry, Genetics and Molecular Biology | 4 | 10% |
| Chemical Engineering | 1 | 3% |
| Veterinary Science and Veterinary Medicine | 1 | 3% |
| Other | 3 | 8% |
| Unknown | 11 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 June 2012.
All research outputs
#14,146,599
of 22,668,244 outputs
Outputs from Breast Cancer Research and Treatment
#3,042
of 4,615 outputs
Outputs of similar age
#98,137
of 166,794 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#33
of 42 outputs
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