Evidence map›Paper›PMID 34347086›Full record

ArticleNeuro-oncology2022

Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice.

Pavlina Chuntova, Yafei Hou, Ryosuke Naka, Akane Yamamichi, Tiffany Chen, Yitzhar Goretsky, Ryusuke Hatae, Takahide Nejo, Gary Kohanbash, Abigail L Mende and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 2 pooled it
1.0field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
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  15. Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models.International journal of molecular sciences · 2022
    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

17 authors at 2 institutions in 2 countries.

Pavlina ChuntovaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Yafei HouDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Ryosuke NakaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Akane YamamichiDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Tiffany ChenDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Yitzhar GoretskyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Ryusuke HataeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0001-5636-8064
Takahide NejoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Gary KohanbashDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Abigail L MendeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Megan MontoyaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Kira M DowneyDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
David DieboldDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Jayne SkinnerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Hong-Erh LiangDepartment of Medicine, University of California, San Francisco, San Francisco, California, USA.
Bjoern SchwerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Hideho OkadaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID 0000-0003-0076-9920
University of California, San Francisco · USUniversity of Pittsburgh · US

Funding

Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Preclinical development of breakthrough immunotherapy for brain tumorsR35NS105068 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2018 to 2025
$6.0M
NCI NIH HHS T32 CA151022NINDS NIH HHS R35 NS105068
6 · The paper itself

Abstract

backgroundRigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART) cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII).

methodsWe first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T cells and evaluated the function of the CART cells both in vitro and in vivo. To inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208).

resultsBoth RV- and Tg-CART cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII- SB28.

conclusionOur new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies.

Indexed as

ErbB ReceptorsGlioblastomaImmunotherapy, AdoptiveReceptors, Chimeric AntigenAnimalsCell Line, TumorMiceMice, Inbred C57BLMice, Transgenicepidermal growth factor receptor VIIIErbB ReceptorsReceptors, Chimeric AntigenCART cellsEGFRvIIIglioblastomaimmunotherapytransgenic

Identifiers

PMID34347086
PMCPMC8804899
OpenAlexW3188482034

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.