Evidence map›Paper›PMID 31248461›Full record

Trial reportJournal for immunotherapy of cancer2019

A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund's adjuvant in melanoma patients.

Marit M Melssen, Gina R Petroni, Kimberly A Chianese-Bullock, Nolan A Wages, William W Grosh, Nikole Varhegyi, Mark E Smolkin, Kelly T Smith, Nadejda V Galeassi, Donna H Deacon and 2 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01585350 (A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients, With Evaluation of the Injection Site Microenvironment), which is not on this map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.8field-weighted citation impact, top 6% 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.

NCT01585350 phase1completednot on this map

A Multipeptide Vaccine Plus Toll-Like Receptor Agonists in Melanoma Patients, With Evaluation of the Injection Site Microenvironment

TypeinterventionalSponsorCraig L Slingluff, JrRan2012 to 2014Enrolled53ConditionsMelanomaArmsMELITAC 12.1 + Montanide ISA-51 + lipopolysaccharide (LPS), MELITAC 12.1 + Montanide ISA-51 + polyICLC
3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 96 citations in OpenAlex.

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  6. Pre-Encoded IFN-I Sensitivity Exacerbates Memory T Cell Senescence in Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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3 more citing papers are in PubMed but not listed here.

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

12 authors at 1 institution in 1 country.

Marit M MelssenDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Gina R PetroniDepartment of Public Health Sciences/Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, VA, USA.
Kimberly A Chianese-BullockDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Nolan A WagesDepartment of Public Health Sciences/Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, VA, USA.
William W GroshDepartment of Medicine/Division of Hematology/Oncology, University of Virginia, Charlottesville, VA, USA.
Nikole VarhegyiDepartment of Public Health Sciences/Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, VA, USA.
Mark E SmolkinDepartment of Public Health Sciences/Division of Translational Research & Applied Statistics, University of Virginia, Charlottesville, VA, USA.
Kelly T SmithDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Nadejda V GaleassiDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Donna H DeaconDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Elizabeth M GaughanDepartment of Medicine/Division of Hematology/Oncology, University of Virginia, Charlottesville, VA, USA.
Craig L SlingluffDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Pinn Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA. cls8h@virginia.edu.ORCID 0000-0002-6664-4373
University of Virginia · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
MELANOMA VACCINES USING MHC-ASSOCIATED PEPTIDESR01CA057653 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI SLINGLUFF, CRAIG LEE · 1997 to 2012
$3.4M
Phase I Designs for Combined Immunotherapies in CancerK25CA181638 · NCI · UNIVERSITY OF VIRGINIA · PI WAGES, NOLAN · 2014 to 2018
$780k
NCI NIH HHS K25 CA181638NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA057653
6 · The paper itself

Abstract

backgroundCancer vaccines require adjuvants to induce effective immune responses; however, there is no consensus on optimal adjuvants. We hypothesized that toll-like receptor (TLR)3 agonist polyICLC or TLR4 agonist lipopolysaccharide (LPS), combined with CD4 T cell activation, would support strong and durable CD8 PATIENTS AND

methodsParticipants with resected stage IIB-IV melanoma received a vaccine comprised of 12 melanoma peptides restricted by Class I MHC (12MP), plus a tetanus helper peptide (Tet). Participants were randomly assigned 2:1 to cohort 1 (LPS dose-escalation) or cohort 2 (polyICLC). Each cohort included 3 subgroups (a-c), receiving 12MP + Tet + TLR agonist without IFA (0), or with IFA in vaccine one (V1), or all six vaccines (V6). Toxicities were recorded (CTCAE v4). T cell responses were measured with IFNγ ELIspot assay ex vivo or after one in vitro stimulation (IVS).

resultsFifty-three eligible patients were enrolled, of which fifty-one were treated. Treatment-related dose-limiting toxicities (DLTs) were observed in 0/33 patients in cohort 1 and in 2/18 patients in cohort 2 (11%). CD8 T cell responses to 12MP were detected ex vivo in cohort 1 (42%) and in cohort 2 (56%) and in 18, 50, and 72% for subgroups V0, V1, and V6, respectively. T cell responses to melanoma peptides were more durable and of highest magnitude for IFA V6.

conclusionsLPS and polyICLC are safe and effective vaccine adjuvants when combined with IFA. Contrary to the central hypothesis, IFA enhanced T cell responses to peptide vaccines when added to TLR agonists. Future studies will aim to understand mechanisms underlying the favorable effects with IFA.

trial registrationThe clinical trial Mel58 was performed with IRB (#15781) and FDA approval and is registered with Clinicaltrials.gov on April 25, 2012 (NCT01585350). Patients provided written informed consent to participate. Enrollment started on June 24, 2012.

Indexed as

Adjuvants, ImmunologicCancer VaccinesCarboxymethylcellulose SodiumCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleFreund's AdjuvantHumansLipidsLipopolysaccharidesMaleMelanomaPoly I-CPolylysineToll-Like ReceptorsVaccines, SubunitAdjuvants, ImmunologicCancer VaccinesCarboxymethylcellulose SodiumFreund's Adjuvantincomplete Freund's adjuvantLipidsLipopolysaccharidesPoly I-Cpoly ICLCPolylysineToll-Like ReceptorsVaccines, SubunitCD8 T cellsClinical trialELIspotImmune responseIncomplete freund’s adjuvantLipopolysaccharideMelanomaPeptide vaccinepolyICLCToll-like receptor

Identifiers

PMID31248461
PMCPMC6598303
OpenAlexW2954148017

What OpenQuestion holds

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LicenceCC BY
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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.