Evidence map›Paper›PMID 39420062›Full record

ArticleNature biomedical engineering2024

Targeting overexpressed antigens in glioblastoma via CAR T cells with computationally designed high-affinity protein binders.

Zhen Xia, Qihan Jin, Zhilin Long, Yexuan He, Fuyi Liu, Chengfang Sun, Jinyang Liao, Chun Wang, Chentong Wang, Jian Zheng and 6 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Protein design and RNA design: Perspectives.Quantitative biology (Beijing, China) · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. Editorial: Research on nanomaterials in tumor diagnosis and therapy, volume II.Frontiers in bioengineering and biotechnology · 2026
    Article
  14. Sequence and structural determinants of efficaciousbioRxiv : the preprint server for biology · 2025
    Article
  15. Review
  16. Article
  17. Review
  18. From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Zhen Xia *Westlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Qihan Jin *Westlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Zhilin LongWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Yexuan HeSchool of Life Sciences, Westlake University, Hangzhou, China.
Fuyi LiuDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Chengfang SunWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Jinyang LiaoWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Chun WangDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Chentong WangWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Jian ZhengDepartment of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Weixi ZhaoWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Tianxin ZhangWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
Jeremy N RichUniversity of Pittsburgh Medical Center Hillman Cancer Center, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7845-5302
Yongdeng ZhangSchool of Life Sciences, Westlake University, Hangzhou, China.ORCID http://orcid.org/0000-0002-4569-8137
Longxing CaoWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. caolongxing@westlake.edu.cn.ORCID http://orcid.org/0000-0003-4002-3648
Qi XieWestlake Disease Modeling Laboratory, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. xieqi@westlake.edu.cn.ORCID http://orcid.org/0000-0002-2370-2078

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32150015National Natural Science Foundation of China (National Science Foundation of China) 32370989National Natural Science Foundation of China (National Science Foundation of China) 82073268
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T cells targeting receptors on tumour cells have had limited success in patients with glioblastoma. Here we report the development and therapeutic performance of CAR constructs leveraging protein binders computationally designed de novo to have high affinity for the epidermal growth factor receptor (EGFR) or the tumour-associated antigen CD276, which are overexpressed in glioblastoma. With respect to T cells with a CAR using an antibody-derived single-chain variable fragment as antigen-binding domain, the designed binders on CAR T cells promoted the proliferation of the cells, the secretion of cytotoxic cytokines and their resistance to cell exhaustion, and improved antitumour performance in vitro and in vivo. Moreover, CARs with the binders exhibited higher surface expression and greater resistance to degradation, as indicated by bulk and single-cell transcriptional profiling of the cells. The de novo design of binding domains for specific tumour antigens may potentiate the antitumour efficacy of CAR T cell therapies for other solid cancers.

Indexed as

Antigens, NeoplasmErbB ReceptorsGlioblastomaImmunotherapy, AdoptiveReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorCell ProliferationHumansMiceProtein BindingSingle-Chain AntibodiesAntigens, NeoplasmEGFR protein, humanErbB ReceptorsReceptors, Chimeric AntigenSingle-Chain Antibodies

Identifiers

PMID39420062

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.