Evidence map›Paper›PMID 36045585›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.

Yanting Duan, Jiangqing Chen, Xianhui Meng, Longwei Liu, Kai Shang, Xiaoyan Wu, Yajie Wang, Zihan Huang, Houyu Liu, Yanjie Huang and 4 more

Open access · greenAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

15 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. "Electric power boost" for CAR-T-cell potency.Cellular & molecular immunology · 2025
    Article
  8. Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Joining Forces for Cancer Treatment: From "TCR versus CAR" to "TCR and CAR".International journal of molecular sciences · 2022
    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

14 authors at 4 institutions in 2 countries.

Yanting DuanBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Jiangqing ChenBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Xianhui MengBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Longwei LiuDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Kai ShangBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Xiaoyan WuBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Yajie WangBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Zihan HuangBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Houyu LiuBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China.
Yanjie HuangKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310058, China.
Chun ZhouSchool of Public Health and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
Xiaofei GaoKey Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310058, China.
Yingxiao WangDepartment of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Jie SunBone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; Institute of Hematology, Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310058, Zhejiang, China. Electronic address: sunj4@zju.edu.cn.
Zhejiang University · CNUniversity of California, San Diego · USWestlake University · CNSir Run Run Shaw Hospital · CN

Funding

Role of Spatiotemporal Epigenetic Dynamics in Regulating Endothelial Gene Expressions under FlowsR01HL121365 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHIEN, SHU, WANG, YINGXIAO · 2014 to 2025
$7.5M
Ultrasensitive kinase biosensors for multiplex imaging of coordinated spatiotemporal signaling in cancer-immune interactionsR01CA262815 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Yingxiao Wang, Jin Zhang · 2022 to 2026
$3.3M
Acoustothermogenetics for Cell EngineeringR35GM140929 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WANG, YINGXIAO · 2021 to 2025
$2.9M
Ultrasound-controlled remote activation of CAR T cells for localized tumor immunotherapyR01EB029122 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WANG, YINGXIAO · 2020 to 2023
$1.7M
NHLBI NIH HHS R01 HL121365NIBIB NIH HHS R01 EB029122NIGMS NIH HHS R35 GM140929
6 · The paper itself

Abstract

CD19-targeting chimeric antigen receptors (CARs) with CD28 and CD3ζ signaling domains have been approved by the US FDA for treating B cell malignancies. Mutation of immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3ζ generated a single-ITAM containing 1XX CAR, which displayed superior antitumor activity in a leukemia mouse model. Here, we investigated whether the 1XX design could enhance therapeutic potency against solid tumors. We constructed both CD19- and AXL-specific 1XX CARs and compared their in vitro and in vivo functions with their wild-type (WT) counterparts. 1XX CARs showed better antitumor efficacy in both pancreatic and melanoma mouse models. Detailed analysis revealed that 1XX CAR-T cells persisted longer in vivo and had a higher percentage of central memory cells. With fluorescence resonance energy transfer (FRET)-based biosensors, we found that decreased ITAM numbers in 1XX resulted in similar 70-kDa zeta chain-associated protein (ZAP70) activation, while 1XX induced higher Ca

Indexed as

NeoplasmsReceptors, Chimeric AntigenT-LymphocytesAnimalsCD28 AntigensCell Line, TumorImmunotherapy, AdoptiveMiceXenograft Model Antitumor AssaysCD28 AntigensReceptors, Chimeric Antigen1XXAXLCARCD19CD28CD3ζimmunotherapyITAM

Identifiers

PMID36045585
PMCPMC9840118
OpenAlexW4293767314

What OpenQuestion holds

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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.