Evidence map›Paper›PMID 22130163›Full record

Trial reportJournal of immunotherapy (Hagerstown, Md. : 1997)2012

The vaccine-site microenvironment induced by injection of incomplete Freund's adjuvant, with or without melanoma peptides.

Rebecca C Harris, Kimberly A Chianese-Bullock, Gina R Petroni, Jochen T Schaefer, Louis B Brill, Kerrington R Molhoek, Donna H Deacon, James W Patterson, Craig L Slingluff

Abstract readClinical TrialComparative Study
In one paragraph

Trial report in Journal of immunotherapy (Hagerstown, Md. : 1997), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. Personalized cancer vaccines: adjuvants are important, too.Cancer immunology, immunotherapy : CII · 2018
    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

9 authors.

Rebecca C HarrisDepartment of Surgery, University of Virginia, Charlottesville, VA 22908, USA. cls8h@virginia.edu
Kimberly A Chianese-Bullock
Gina R Petroni
Jochen T Schaefer
Louis B Brill
Kerrington R Molhoek
Donna H Deacon
James W Patterson
Craig L Slingluff

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Thomas P. Loughran · 1987 to 2026
$72.1M
ZACOPRIDE VS METOCLOPRAMIDE--EFFECT ON LOWER ESOPHAGEAL SPHINCTERM01RR000847 · NCRR · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI BRETON, MARC D · 1985 to 2010
$48.1M
INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007496 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Michael G. Brown, Coleen A McNamara · 1995 to 2026
$10.2M
MELANOMA VACCINES USING MHC-ASSOCIATED PEPTIDESR01CA057653 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI SLINGLUFF, CRAIG LEE · 1997 to 2012
$3.4M
Multi-peptide Vaccine Administered with Cyclophosphamide for High-risk MelanomaR01CA118386 · NCI · UNIVERSITY OF VIRGINIA · PI SLINGLUFF, CRAIG LEE · 2006 to 2010
$1.8M
NCI NIH HHS P30 CA044579NCI NIH HHS P30 CA44579NCI NIH HHS R01 CA057653NCI NIH HHS R01 CA118386NCI NIH HHS R01 CA57653NCRR NIH HHS M01 RR000847NCRR NIH HHS M01 RR00847NIAID NIH HHS T32 AI007496
6 · The paper itself

Abstract

Cancer vaccines have not been optimized. They depend on adjuvants to create an immunogenic microenvironment for antigen presentation. However, remarkably little is understood about cellular and molecular changes induced by these adjuvants in the vaccine microenvironment. We hypothesized that vaccination induces dendritic cell (DC) activation in the dermal vaccination microenvironment but that regulatory processes may also limit the effectiveness of repeated vaccination. We evaluated biopsies from immunization sites in 2 clinical trials of melanoma patients. In 1 study (Mel38), patients received 1 injection with an adjuvant mixture alone, composed of incomplete Freund's adjuvant (IFA) plus granulocyte-macrophage colony stimulating factor (GM-CSF). In a second study, patients received multiple vaccinations with melanoma peptide antigens plus IFA. Single injections with adjuvant alone induced dermal inflammatory infiltrates consisting of B cells, T cells, mature DCs, and vessels resembling high endothelial venules (HEVs). These cellular aggregates usually lacked organization and were transient. In contrast, multiple repeated vaccinations with peptides in adjuvant induced more organized and persistent lymphoid aggregates containing separate B and T cell areas, mature DCs, HEV-like vessels, and lymphoid chemokines. Within these structures, there are proliferating CD4and CD8 T lymphocytes, as well as FoxP3CD4 lymphocytes, suggesting a complex interplay of lymphoid expansion and regulation within the dermal immunization microenvironment. Further study of the physiology of the vaccine site microenvironment promises to identify opportunities for enhancing cancer vaccine efficacy by modulating immune activation and regulation at the site of vaccination.

Indexed as

Antigens, NeoplasmB-LymphocytesCancer VaccinesCell CommunicationCell MovementCellular MicroenvironmentCytokinesDendritic CellsForkhead Transcription FactorsFreund's AdjuvantGranulocyte-Macrophage Colony-Stimulating FactorHumansImmunization, SecondaryImmunomodulationInjections, IntradermalLipidsAntigens, NeoplasmCancer VaccinesCytokinesForkhead Transcription FactorsFOXP3 protein, humanFreund's AdjuvantGranulocyte-Macrophage Colony-Stimulating Factorincomplete Freund's adjuvantLipidsPeptide Fragments

Identifiers

PMID22130163
PMCPMC3282210

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.