Evidence map›Paper›PMID 34675920›Full record

ArticleFrontiers in immunology2021

Reducing Hinge Flexibility of CAR-T Cells Prolongs Survival

Ang Zhang, Yao Sun, Jie Du, Yansheng Dong, Honggang Pang, Lei Ma, Shaoyan Si, Zhong Zhang, Mingyi He, Yang Yue and 6 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Frontiers in immunology · 2026
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  11. Chimeric antigen receptor therapies: Development, design, and implementation.The Journal of allergy and clinical immunology · 2025
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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

16 authors.

Ang ZhangDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Yao SunDepartment of Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Jie DuSAFE Pharmaceutical Research Institute Co. Ltd, HeBei, China.
Yansheng DongSAFE Pharmaceutical Research Institute Co. Ltd, HeBei, China.
Honggang PangDepartment of Emergency, Affiliated Zhongshan Hospital, Dalian University, Dalian, China.
Lei MaAcademy of Military Medical Sciences, Academy of Military Sciences, Beijing, China.
Shaoyan SiDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Zhong ZhangDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Mingyi HeDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Yang YueDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Xiaoli ZhangDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Weichao ZhaoDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Jianjun PiDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.
Mindong ChangStrategic Support Force Medical Center, The Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Quanjun WangNational Beijing Center for Drug Safety Evaluation and Research, State Key Laboratory of Medical Countermeasures and Toxicology, Institute of Pharmacology and Toxicology, Academy of Military Sciences, Beijing, China.
Yikun ZhangDepartment of Hematology, Strategic Support Force Medical Center, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in B cell malignancies. However, high tumor burden limits clinical efficacy and increases the risk of cytokine release syndrome and neurotoxicity, which is associated with over-activation of the CAR-T cells. The hinge domain plays an important role in the function of CAR-T cells. We hypothesized that deletion of glycine, an amino acid with good flexibility, may reduce the flexibility of the hinge region, thereby mitigating CAR-T cell over-activation. This study involved generating a novel CAR by deletion of two consecutive glycine residues in the CD8 hinge domain of second-generation (2nd) CAR, thereafter named 2nd-GG CAR. The 2nd-GG CAR-T cells showed similar efficacy of CAR expression but lower hinge flexibility, and its protein affinity to CD19 protein was lower than that of 2nd CAR-T cells. Compared to the 2nd CAR-T cells, 2nd-GG CAR-T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells

Indexed as

AnimalsAntigens, CD19CD8 AntigensCell Line, TumorCytokinesFemaleHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellLymphocyte TransfusionMiceMice, SCIDReceptors, Chimeric AntigenSurvival AnalysisT-LymphocytesTransduction, GeneticAntigens, CD19CD8alpha antigenCD8 AntigensCytokinesReceptors, Chimeric Antigencellular immunotherapychimeric antigen receptor (CAR T)cytokine release storm (CRS)gene modified T cellhinge regionstructure optimization

Identifiers

PMID34675920
PMCPMC8524077

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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.