Evidence map›Paper›PMID 38607370›Full record

ArticleThe Journal of experimental medicine2024

Self-regulating CAR-T cells modulate cytokine release syndrome in adoptive T-cell therapy.

Meng-Yin Lin, Eunwoo Nam, Ryan M Shih, Amanda Shafer, Amber Bouren, Melanie Ayala Ceja, Caitlin Harris, Mobina Khericha, Kenny H Vo, Minsoo Kim and 2 more

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

Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
9.0field-weighted citation impact, top 1% 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

27 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026
    Review
  3. Article
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  12. Article
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  14. Article
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  17. Precision sniper for solid tumors: CAR-NK cell therapy.Cancer immunology, immunotherapy : CII · 2025
    Review
  18. Review
  19. Article
  20. 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

12 authors at 1 institution in 1 country.

Meng-Yin LinDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0009-0009-0700-848X
Eunwoo NamDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0001-9507-1415
Ryan M ShihDepartment of Molecular Biology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-3570-867X
Amanda ShaferDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2931-1569
Amber Bouren *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0009-0004-0385-3276
Melanie Ayala Ceja *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-2906-5786
Caitlin Harris *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-2325-1729
Mobina Khericha *Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-6734-7741
Kenny H VoDepartment of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-3760-6124
Minsoo KimDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-0462-8092
Chi-Hong TsengDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-2549-6167
Yvonne Y ChenDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-5583-119X
University of California, Los Angeles · US

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2M
NCI NIH HHS P50 CA211015NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration. Unexpectedly, Toci-secreting CD19 CAR-T cells exhibit superior in vivo antitumor efficacy compared with conventional CD19 CAR-T cells. scRNA-seq analysis of immune cells recovered from tumor-bearing humanized mice revealed treatment with Toci-secreting CD19 CAR-T cells enriches for cytotoxic T cells while retaining memory T-cell phenotype, suggesting Toci secretion not only reduces toxicity but also significantly alters the overall T-cell composition. This approach of engineering T cells to self-regulate inflammatory cytokine production is a clinically compatible strategy with the potential to simultaneously enhance safety and efficacy of CAR-T cell therapy for cancer.

Indexed as

Cytokine Release SyndromeCytokinesAdaptor Proteins, Signal TransducingAnimalsAntigens, CD19Cell- and Tissue-Based TherapyMiceAdaptor Proteins, Signal TransducingAntigens, CD19Cytokines

Identifiers

PMID38607370
PMCPMC11010356
OpenAlexW4394762883

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.