Evidence map›Paper›PMID 37934007›Full record

ArticleCancer discovery2024

Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function.

Nayan Jain, Zeguo Zhao, Richard P Koche, Chenling Antelope, Yosi Gozlan, Antonino Montalbano, David Brocks, Michael Lopez, Anton Dobrin, Yuzhe Shi and 3 more

Open access · greenAbstract read
In one paragraph

Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
16.3field-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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  7. Decoding T cell exhaustion in the tumour microenvironment.Experimental & molecular medicine · 2026
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  10. Special Issue "State-of-the-Art Cancer Immunotherapies-2nd Edition".International journal of molecular sciences · 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

13 authors at 3 institutions in 2 countries.

Nayan Jain *Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-9910-4824
Zeguo Zhao *Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-2901-5033
Richard P KocheCenter for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-6820-5083
Chenling AntelopeImmunai, New York, New York.ORCID 0000-0001-9610-7627
Yosi GozlanImmunai, New York, New York.ORCID 0009-0006-3816-3798
Antonino MontalbanoImmunai, New York, New York.ORCID 0000-0002-7824-342X
David BrocksImmunai, New York, New York.ORCID 0000-0002-9369-8772
Michael LopezCenter for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0001-5691-5272
Anton DobrinLouis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-9751-0677
Yuzhe ShiCenter for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0009-8483-0418
Gertrude GunsetCenter for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0009-0002-2715-6980
Theodoros GiavridisMnemo Therapeutics, New York, New York.ORCID 0000-0002-8716-781X
Michel SadelainCenter for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0002-9031-8025
Memorial Sloan Kettering Cancer Center · USInstitute of Neuroimmunology of the Slovak Academy of Sciences · SKCarmot Therapeutics (United States) · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
The Memorial Sloan Kettering Cancer Center SPORE in LeukemiaP50CA254838 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Eytan Stein · 2021 to 2026
$16.8M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA254838
6 · The paper itself

Abstract

Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies. SIGNIFICANCE: T cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells. See related article by López-Cobo et al., p. 120. This article is featured in Selected Articles from This Issue, p. 5.

Indexed as

LeukemiaReceptors, Chimeric AntigenCD28 AntigensHistonesHumansImmunotherapy, AdoptiveMaleMethylationMethyltransferasesReceptors, Antigen, T-CellRepressor ProteinsT-LymphocytesXenograft Model Antitumor AssaysCD28 AntigensHistonesMethyltransferasesReceptors, Antigen, T-CellReceptors, Chimeric AntigenRepressor ProteinsSUV39H1 protein, human

Identifiers

PMID37934007
PMCPMC10880746
OpenAlexW4388464258

What OpenQuestion holds

Textmetadata
LicenceTDM
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.