Evidence map›Paper›PMID 39797399›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

The high efficacy of claudin18.2-targeted CAR-T cell therapy in advanced pancreatic cancer with an antibody-dependent safety strategy.

Guocheng Zhong, Xiaomin Zhang, Ruocong Zhao, Zheng Guo, Chenguang Wang, Chuan Yu, Dongzhe Liu, Ke Hu, Yujie Gao, Bochen Zhao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. CAR-T cell therapy targeting MUC17 in gastric tumors.Journal for immunotherapy of cancer · 2025
    Article
  6. Review
  7. Article
  8. Article
  9. CAR T-Cell Therapy in Cancer: Balancing Efficacy with Cardiac Toxicity Concerns.Journal of cancer science and clinical therapeutics · 2025
    Article
  10. 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

15 authors.

Guocheng ZhongDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Xiaomin ZhangDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China.
Ruocong ZhaoDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China.
Zheng GuoDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Chenguang WangDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China.
Chuan YuShenzhen Haoshi Biotechnology Company, Shenzhen, China; Shenzhen University-Haoshi Cell Therapy Institute, Shenzhen, China.
Dongzhe LiuDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Ke HuDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Yujie GaoDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Bochen ZhaoDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Xianhao LiuDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Xuanren ShiDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Lei ChenDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.
Yisheng LiShenzhen Haoshi Biotechnology Company, Shenzhen, China; Shenzhen University-Haoshi Cell Therapy Institute, Shenzhen, China. Electronic address: ysli@haoshibio.com.
Li YuDepartment of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Shenzhen Key Laboratory, Hematology Institution of Shenzhen University, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China; Shenzhen University-Haoshi Cell Therapy Institute, Shenzhen, China. Electronic address: yuli@szu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Claudin18.2 is highly expressed in PC tissue and could serve as a suitable target for CAR-T therapy. In the present study, we reported the utilization of tEGFR-expressing claudin18.2-targeted CAR-T cells to treat 3 patients with advanced PC. Intriguingly, all 3 patients achieved disease remission after CAR-T cell infusion, with 1 complete remission (CR) and 2 partial remissions (PRs). However, gastric mucosal injury was observed, which was recognized as on-target off-tumor toxicity (OTOT) and may be due to the expression of claudin18.2 on normal gastric tissues. To control the severe OTOT in patient 3, cyclophosphamide and cetuximab were administered to deplete CAR-T cells, and they successfully controlled OTOT. Single-cell transcriptome and T cell receptor sequencing revealed the objective alterations of CAR-T cell clones after cetuximab treatment. Collectively, the present study showed the robust anti-tumor activity of claudin18.2-targeted CAR-T cells against PC and reported the feasibility of the antibody-dependent safety switch strategy to control the OTOT caused by CAR-T cells in patients. Our study may pave the way for the development of a novel strategy to treat patients with advanced PC in the future.

Indexed as

ClaudinsImmunotherapy, AdoptivePancreatic NeoplasmsReceptors, Chimeric AntigenT-LymphocytesAgedCell Line, TumorCetuximabFemaleHumansMaleMiddle AgedTreatment OutcomeCetuximabClaudinsCLDN18 protein, humanReceptors, Chimeric Antigenadvanced pancreatic cancerCAR-T cell therapycetuximabclaudin18.2EGFR

Identifiers

PMID39797399
PMCPMC12172178

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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.