Evidence map›Paper›PMID 39196413›Full record

ArticleCellular and molecular life sciences : CMLS2024

A novel bispecific T-cell engager using the ligand-target csGRP78 against acute myeloid leukemia.

Xiaozhu Zeng, Hang Zhang, Jing Guo, Dong Yang, Yongjie Zhu, Nan Liu, Jie Tang, Ting Liu, Xudong Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. 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

9 authors.

Xiaozhu Zeng *Department of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Hang Zhang *Department of Hematology, Institute of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.
Jing GuoDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Dong YangDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Yongjie ZhuDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Nan LiuDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Jie TangDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Ting LiuDepartment of Hematology, Institute of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China. liuting@scu.edu.cn.
Xudong ZhaoDepartment of Targeting Therapy & Immunology and Laboratory of Animal Tumor Models, Cancer Center and State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. zhaoxudong@wchscu.cn.ORCID http://orcid.org/0000-0001-9126-7365

Funding

National Natural Science Foundation of China 82172701Sichuan Science and Technology Program 2024YFHZ0063the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University ZYYC20002
6 · The paper itself

Abstract

Current medical therapies for treating acute myeloid leukemia (AML) remain unmet, and AML patients may benefit from targeted immunotherapy approaches that focus on specific tumor antigens. GRP78, which is upregulated in various malignant tumors such as AML, is partially expressed as cell surface GRP78 (csGRP78) on the cell membrane, making it an ideal target for redirecting T cells, including T-cell engagers. However, considering the conventional approach of using two scFv segments to construct a bispecific T-cell engager (BiTE), we have undertaken the development of a novel BiTE that utilizes a cyclic peptide ligand to specifically target csGRP78, which we refer to as GRP78-CD3/BiTE. We studied the effects of GRP78-CD3/BiTE on treatments for AML in vitro and in vivo and assessed the pharmacokinetics of this engager. Our findings demonstrated that GRP78-CD3/BiTE could not only effectively mediate the cytotoxicity of T cells against csGRP78-expressing AML cells but also specifically eliminate primary AML tumor cells in vitro. Furthermore, GRP78-CD3/BiTE exhibited a longer half-life despite having a lower molecular weight than CD19-CD3/BiTE. In a xenograft mouse model of AML, treatment with GRP78-CD3/BiTE prolonged the survival time of the mice. Our findings demonstrate that GRP78-CD3/BiTE is effective and selective for eliminating csGRP78-expressing AML cells and suggest that this approach to targeted immunotherapy could lead to effective new treatments for AML.

Indexed as

Antibodies, BispecificEndoplasmic Reticulum Chaperone BiPLeukemia, Myeloid, AcuteT-LymphocytesAnimalsCD3 ComplexCell Line, TumorFemaleHeat-Shock ProteinsHumansImmunotherapyLigandsMiceMice, Inbred NODMice, SCIDXenograft Model Antitumor AssaysAntibodies, BispecificCD3 ComplexEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHSPA5 protein, humanHspa5 protein, mouseLigandsAMLBispecific T-cell engagerscsGRP78Pep42

Identifiers

PMID39196413
PMCPMC11358366

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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.