Evidence map›Paper›PMID 22678162›Full record

ArticleBreast cancer research and treatment2013

Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells.

Venkataswarup Tiriveedhi, Timothy P Fleming, Peter S Goedegebuure, Michael Naughton, Cynthia Ma, Craig Lockhart, Feng Gao, William E Gillanders, T Mohanakumar

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research and treatment, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.3field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
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  20. Cancer DNA vaccines: current preclinical and clinical developments and future perspectives.Journal of experimental & clinical cancer research : CR · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Venkataswarup TiriveedhiDepartment of Surgery, Washington University School of Medicine, Box 8109-3328 CSRB, 660 South Euclid Avenue, Saint Louis, MO 63110, USA.
Timothy P Fleming
Peter S Goedegebuure
Michael Naughton
Cynthia Ma
Craig Lockhart
Feng Gao
William E Gillanders
T Mohanakumar
Washington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
NCI NIH HHS P30 CA091842
6 · The paper itself

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.

Indexed as

Breast NeoplasmsCancer VaccinesCD4-Positive T-LymphocytesDNA, ComplementaryFemaleForkhead Transcription FactorsHumansInducible T-Cell Co-Stimulator ProteinInterferon-gammaInterleukin-10Lymphocyte CountMammaglobin AT-Lymphocytes, CytotoxicVaccines, DNACancer VaccinesDNA, ComplementaryForkhead Transcription FactorsFOXP3 protein, humanInducible T-Cell Co-Stimulator ProteinInterferon-gammaInterleukin-10Mammaglobin AVaccines, DNA

Identifiers

PMID22678162
PMCPMC3656506
OpenAlexW2014572446

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.