Evidence map›Paper›PMID 28716080›Full record

ArticleJournal for immunotherapy of cancer2017

Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination.

Laura E Johnson, Brian M Olson, Douglas G McNeel

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00582140 (Phase I Study of a DNA-based Vaccine Targeting Prostatic Acid Phosphatase), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 28% 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.

NCT00582140 phase1completednot on this map

Phase I Study of a DNA-based Vaccine Targeting Prostatic Acid Phosphatase (PAP) in Patients With Stage D0 Prostate Cancer

TypeinterventionalSponsorUniversity of Wisconsin, MadisonRan2005 to 2008Enrolled22ConditionsProstate CancerArmspTVG-HP with rhGM-CSF
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
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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

3 authors at 1 institution in 1 country.

Laura E JohnsonUniversity of Wisconsin Carbone Cancer Center, 7007 Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI, 53705, USA.
Brian M OlsonUniversity of Wisconsin Carbone Cancer Center, 7007 Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI, 53705, USA.
Douglas G McNeelUniversity of Wisconsin Carbone Cancer Center, 7007 Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI, 53705, USA. dm3@medicine.wisc.edu.
University of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
NCI NIH HHS P30 CA014520
6 · The paper itself

Abstract

backgroundImmunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers.

methodsPatients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model.

resultsThe frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016).

conclusionsWhile our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

Indexed as

Acid PhosphataseAnimalsAntigens, NeoplasmBiomarkers, TumorCancer VaccinesHumansImmunity, CellularImmunogenicity, VaccineImmunophenotypingInterferon-gammaInterleukin-10Leukocyte CountLeukocytes, MononuclearMaleMice, SCIDProstatic NeoplasmsAcid PhosphataseAntigens, NeoplasmBiomarkers, TumorCancer VaccinesInterferon-gammaInterleukin-10prostatic acid phosphataseVaccines, DNABiomarkerDNA vaccineInterleukin 10Prostate cancerProstatic acid phosphatase

Identifiers

PMID28716080
PMCPMC5514519
OpenAlexW2729927816

What OpenQuestion holds

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Registered trials

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.