Evidence map›Paper›PMID 32133512›Full record

ArticleNeuro-oncology2020

Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine.

Connor J Liu, Maximilian Schaettler, Dylan T Blaha, Jay A Bowman-Kirigin, Dale K Kobayashi, Alexandra J Livingstone, Diane Bender, Christopher A Miller, David M Kranz, Tanner M Johanns and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Translational Theranostics in Glioblastoma: FAPI-46 as a Precision Medicine Tool.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
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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

11 authors at 4 institutions in 1 country.

Connor J LiuDepartment of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri.
Maximilian SchaettlerDepartment of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri.
Dylan T BlahaDepartment of Biochemistry, University of Illinois, Urbana, Illinois.
Jay A Bowman-KiriginDepartment of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri.
Dale K KobayashiDepartment of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri.
Alexandra J LivingstoneDivision of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
Diane BenderAndrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, Missouri.
Christopher A MillerThe McDonnell Genome Institute, Washington University in St Louis, St Louis, Missouri.
David M KranzDepartment of Biochemistry, University of Illinois, Urbana, Illinois.
Tanner M JohannsAndrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, Missouri.
Gavin P DunnDepartment of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri.
Washington University in St. Louis · USNeurological Surgery · USUniversity of Illinois Urbana-Champaign · USBarnes-Jewish Hospital · US

Funding

TRAINING PROGRAM IN IMMUNOLOGY AND IMMUNOGENETICST32AI007163 · NIAID · WASHINGTON UNIVERSITY · PI Kenneth M Murphy, Kodi S Ravichandran · 1985 to 2026
$14.8M
Targeting Neoantigens in GlioblastomaR01NS112712 · NINDS · WASHINGTON UNIVERSITY · PI DUNN, GAVIN PETER · 2019 to 2024
$2.3M
Engineering T Cell Receptors for Adoptive Cell TherapiesR01CA178844 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KRANZ, DAVID M. · 2014 to 2018
$1.6M
IMMUNOBIOLOGY OF MALIGNANT GLIOMAK08NS092912 · NINDS · WASHINGTON UNIVERSITY · PI DUNN, GAVIN PETER · 2015 to 2019
$877k
Autochthonous and Ex-vivo Derived Mouse Models of Malignant GliomaF30CA236454 · NCI · WASHINGTON UNIVERSITY · PI BOWMAN-KIRIGIN, JAY AARON · 2019 to 2021
$129k
NCI NIH HHS F30 CA236454NCI NIH HHS R01 CA178844NIAID NIH HHS T32 AI007163NINDS NIH HHS K08 NS092912NINDS NIH HHS R01 NS112712
6 · The paper itself

Abstract

backgroundAlthough clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed "neoantigens," represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination.

methodsFlow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TILs). Whole-exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite, and top-ranking candidates were screened for reactivity by interferon-gamma enzyme linked immunospot assays. Survival analysis was performed comparing neoantigen vaccination, anti-programmed cell death ligand 1 (αPD-L1), or combination therapy.

resultsCompared with the GL261 model, CT2A exhibited immunologic features consistent with human GBM including reduced αPD-L1 sensitivity and hypofunctional TILs. Of the 29 CT2A neoantigens screened, we identified neoantigen-specific CD8+ T-cell responses in the intracranial TIL and draining lymph nodes to two H2-Kb restricted (Epb4H471L and Pomgnt1R497L) and one H2-Db restricted neoantigen (Plin2G332R). Survival analysis showed that therapeutic neoantigen vaccination with Epb4H471L, Pomgnt1R497L, and Plin2G332R, in combination with αPD-L1 treatment was superior to αPD-L1 alone.

conclusionsWe identified endogenous neoantigen specific CD8+ T cells within an αPD-L1 resistant murine GBM and show that neoantigen vaccination significantly augments survival benefit in combination with αPD-L1 treatment. These observations provide important preclinical correlates for GBM immunotherapy trials and support further investigation into the effects of multimodal immunotherapeutic interventions on antiglioma immunity. KEY POINTS: 1. Neoantigen vaccines combined with checkpoint blockade may be promising treatments.2. CT2A tumors exhibit features of human GBM microenvironments.3. Differential scanning fluorimetry assays may complement in silico neoantigen prediction tools.

Indexed as

GlioblastomaAnimalsAntigens, NeoplasmCD8-Positive T-LymphocytesHumansImmunotherapyLymphocytes, Tumor-InfiltratingMiceTumor MicroenvironmentVaccines, CombinedAntigens, NeoplasmVaccines, Combinedglioblastomaimmunogenomicsneoantigenpersonalized vaccination

Identifiers

PMID32133512
PMCPMC7523441
OpenAlexW3010265110

What OpenQuestion holds

Textmetadata
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.