Evidence map›Paper›PMID 40376677›Full record

ArticleNeuro-oncology advances

Comparative evaluation of CAR-expressing T-, NK-, NKT-cells, and macrophages in an immunocompetent mouse glioma model.

Ryusuke Hatae, Payal B Watchmaker, Akane Yamamichi, Keith Kyewalabye, Kaori Okada, Su Phyu, Yitzhar Goretsky, Jeffrey Haegelin, Psalm Pineo-Cavanaugh, Marco Gallus and 7 more

Abstract read
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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

8 citing papers in PubMed.

  1. Review
  2. IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026
    Article
  4. Review
  5. Review
  6. Facts and Hopes of Chimeric Antigen Receptor-Redirected NK T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Review
  7. Review
  8. Review
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.

Ryusuke HataeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0001-5636-8064
Payal B WatchmakerDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-0944-3890
Akane YamamichiDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-8141-7339
Keith KyewalabyeDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Kaori OkadaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Su PhyuDepartment 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.
Jeffrey HaegelinDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Psalm Pineo-CavanaughDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-1521-1607
Marco GallusDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Lan PhungDepartment 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.
Haoyu LongDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Pavlina ChuntovaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-5356-9909
David H RauletDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.ORCID https://orcid.org/0000-0002-1257-8649
Masaki TerabeNeuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA.ORCID https://orcid.org/0000-0002-1777-0189
Hideho OkadaThe Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.ORCID https://orcid.org/0000-0003-0076-9920

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Preclinical development of breakthrough immunotherapy for brain tumorsR35NS105068 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI OKADA, HIDEHO · 2018 to 2025
$6.0M
Mechanisms underlying combination therapy mobilizing NK cellsR01CA270790 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI DAVID H RAULET · 2022 to 2026
$2.3M
NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA270790NINDS NIH HHS R35 NS105068
6 · The paper itself

Abstract

Background: While chimeric antigen receptor (CAR) T-cells are promising, there is a rapidly growing interest in developing other CAR-expressing immune cells. However, to date, no reported studies evaluated these cells side-by-side in immune-competent glioma models. Methods: We developed a novel C57BL/6-background transgenic mouse strain with all hematopoietic cells carrying the anti-epidermal growth factor receptor (EGFR)vIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. Crossing with mice transgenic for Vav-Cre allowed the expression of anti-EGFRvIII CAR in all hematopoietic cells. In particular, we evaluated CAR-T, CAR-NKT, CAR-NK-cells, and CAR-macrophages in a syngeneic mouse SB28EGFRVIII glioma model. Results: CAR-NK and CAR-NKT-cells demonstrated anti-tumor effects comparable to CAR-T cells in vitro. A single intratumoral administration of CAR-T and CAR-NKT cells in combination mediated superior therapeutic efficacy compared to CAR-T cells or CAR-NKT-cells alone. A single intravenous infusion of CAR-NK cells following lymphodepletion failed to mediate significant anti-glioma effects. Additionally, intratumoral injection of CAR-NK cells did not confer therapeutic benefit. Contrary to previous reports using human macrophages, CAR-macrophages did not demonstrate enhanced antigen-presentation activity against glioma cells compared to non-CAR macrophages. Intratumorally administered CAR-macrophages failed to demonstrate local persistence or anti-tumor effects in vivo. Conclusions: These data provide a valuable basis as to which immune cells can mediate effective anti-glioma response in an immuno-competent glioma environment. Our data also suggest that a combination of CAR-T and CAR-NKT-cells may represent a promising therapeutic strategy.

Indexed as

CAR-macrophageCAR-NK cellsCAR-NKT cellscombination CAR therapyglioma syngeneic mouse models

Identifiers

PMID40376677
PMCPMC12080550

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Registered trials

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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.