Evidence map›Paper›PMID 41564857›Full record

ArticleCell reports. Medicine2026

c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors.

Hyatt Balke-Want, Vimal Keerthi, Maria Del Carmen Arenas, Yiyun Chen, Meena Malipatlolla, Dorota D Klysz, Peng Xu, Katie Ho, Kyle Asano, David Stahl and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Engineering T cell therapies for lung cancer.Molecular therapy. Oncology · 2026
    Article
  3. Article
  4. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    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

26 authors.

Hyatt Balke-WantCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany; Cancer Center Cologne Essen (CCCE), Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Vimal KeerthiCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Maria Del Carmen ArenasCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Yiyun ChenCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Meena MalipatlollaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Dorota D KlyszCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Peng XuCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Katie HoCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Kyle AsanoCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
David StahlDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.
Jing HuangCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Aidan RetherfordCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Sunny PatelCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Carley FowlerCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Lukas MaasUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Translational Genomics, Cologne, Germany.
Nikolaos Gkitsas-LongCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Qiaoshi JiangCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Xikun LiuCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Roland UllrichDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany.
Julie GeorgeUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Translational Genomics, Cologne, Germany.
Sabine HeitzenederCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Ramya TunuguntlaCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
Julien SageDepartments of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Elena SotilloCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA.
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA; Division of Pediatric Hematology/Oncology and Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA; Division of Blood and Marrow Transplantation and Cell Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cmackall@stanford.edu.
Steven A FeldmanCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University, Stanford, CA, USA; Weill West Coast Cancer Hub, Stanford, CA, USA; Division of Blood and Marrow Transplantation and Cell Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Laboratory for Cell and Gene Medicine, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: feldmans@stanford.edu.

Funding

Next Generation Immunotherapies for Pediatric CancersR35CA283888 · NCI · STANFORD UNIVERSITY · PI Crystal Mackall · 2024 to 2026
$2.8M
NCI NIH HHS R35 CA283888
6 · The paper itself

Abstract

Small cell lung cancer (SCLC), a highly lethal disease, limits T cell responses by downregulating major histocompatibility (MHC) class I molecules. Because chimeric antigen receptor (CAR) T cells are not MHC restricted, they may provide a powerful strategy against SCLC. However, few CAR targets for SCLC are known. Here, we show that B7-H3/CD276 is expressed in SCLC and thoracic SMARCA4-deficient undifferentiated tumors (UTs) that can clinicopathologically mimic SCLC. Thoracic SMARCA4-deficient UTs limit killing by B7-H3 CAR T cells via secretion of transforming growth factor β1 (TGF-β1). To overcome tumor-driven CAR T cell suppression, we knock in c-JUN alongside a B7-H3 CAR into the TRAC locus of primary human T cells utilizing CRISPR-Cas9. Non-viral c-JUN+B7-H3 CAR T cells show enhanced killing of both SCLC cells with low antigen density and thoracic SMARCA4-deficient UTs, providing a platform to address these highly aggressive entities. We also provide evidence that good manufacturing practice (GMP) clinical-scale manufacturing is feasible for c-JUN+B7-H3 CAR T cells.

Indexed as

Immunotherapy, ActiveLung NeoplasmsProto-Oncogene Proteins c-junSmall Cell Lung CarcinomaAnimalsB7 AntigensCell Line, TumorCRISPR-Cas SystemsDNA HelicasesFemaleGene Knock-In TechniquesHumansMaleMiceNuclear ProteinsPrimary Cell CultureB7 AntigensCD276 protein, humanDNA HelicasesNuclear ProteinsProto-Oncogene Proteins c-junReceptors, Chimeric AntigenSMARCA4 protein, humanTranscription FactorsB7-H3cell therapy scalingCRISPR knock-innon-viral CAR T-cellssmall cell lung cancerthoracic SMARCA4-deficient undifferentiated tumortransforming growth factor-beta 1

Identifiers

PMID41564857
PMCPMC12866126

What OpenQuestion holds

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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.