Evidence map›Paper›PMID 36418477›Full record

ReviewNature reviews. Clinical oncology2023

Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.

Christian L Flugel, Robbie G Majzner, Giedre Krenciute, Gianpietro Dotti, Stanley R Riddell, Dimitrios L Wagner, Mohamed Abou-El-Enein

Open access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 337 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
337citing papers in PubMed, 1 pooled it
42.6field-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

337 citing papers in PubMed, 1 synthesis or guideline pooled it, 469 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
    Pooled it
  2. Trial
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  4. Review
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  6. Article
  7. Review
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  9. CD97/Cells · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

277 more citing papers are in PubMed but not listed here.

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

7 authors at 6 institutions in 2 countries.

Christian L FlugelDivision of Medical Oncology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-8212-9996
Robbie G MajznerDepartment of Paediatrics, Stanford University School of Medicine, Stanford, CA, USA.
Giedre KrenciuteDepartment of Bone Marrow Transplantation and Cellular Therapy, St Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0003-4335-0644
Gianpietro DottiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Stanley R RiddellFred Hutchinson Cancer Research Center, Seattle, WA, USA.
Dimitrios L Wagner *BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-2189-3579
Mohamed Abou-El-Enein *Division of Medical Oncology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. abouelenein@med.usc.edu.ORCID 0000-0003-2903-9040
University of Southern California · USHumboldt-Universität zu Berlin · DEStanford Medicine · USSt. Jude Children's Research Hospital · USUniversity of North Carolina at Chapel Hill · USUniversity of Washington · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Improving genetically engineered T cells for medulloblastomasR01NS121249 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KRENCIUTE, GIEDRE · 2021 to 2025
$2.2M
NCI NIH HHS P30 CA014089NINDS NIH HHS R01 NS121249
6 · The paper itself

Abstract

Therapies with genetically modified T cells that express chimeric antigen receptors (CARs) specific for CD19 or B cell maturation antigen (BCMA) are approved to treat certain B cell malignancies. However, translating these successes into treatments for patients with solid tumours presents various challenges, including the risk of clinically serious on-target, off-tumour toxicity (OTOT) owing to CAR T cell-mediated cytotoxicity against non-malignant tissues expressing the target antigen. Indeed, severe OTOT has been observed in various CAR T cell clinical trials involving patients with solid tumours, highlighting the importance of establishing strategies to predict, mitigate and control the onset of this effect. In this Review, we summarize current clinical evidence of OTOT with CAR T cells in the treatment of solid tumours and discuss the utility of preclinical mouse models in predicting clinical OTOT. We then describe novel strategies being developed to improve the specificity of CAR T cells in solid tumours, particularly the role of affinity tuning of target binders, logic circuits and synthetic biology. Furthermore, we highlight control strategies that can be used to mitigate clinical OTOT following cell infusion such as regulating or eliminating CAR T cell activity, exogenous control of CAR expression, and local administration of CAR T cells.

Indexed as

NeoplasmsReceptors, Chimeric AntigenAnimalsB-Cell Maturation AntigenHumansImmunotherapy, AdoptiveMiceReceptors, Antigen, T-CellT-LymphocytesB-Cell Maturation AntigenReceptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID36418477
PMCPMC10278599
OpenAlexW4309889967

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.