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双特异性抗体在非小细胞肺癌治疗中的应用及未来前景

Application and future prospects of bispecific antibodies in the treatment of non-small cell lung cancer.

作者信息

Wen Junxu, Cui Wenxing, Yin Xiaoyan, Chen Yu, Liu Ailing, Wang Qian, Meng Xiangjiao

机构信息

Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.

出版信息

Cancer Biol Med. 2025 Apr 7;22(4):348-75. doi: 10.20892/j.issn.2095-3941.2024.0470.


DOI:10.20892/j.issn.2095-3941.2024.0470
PMID:40192238
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12032835/
Abstract

As the leading cause of cancer-related deaths, lung cancer remains a noteworthy threat to human health. Although immunotherapies, such as immune checkpoint inhibitors (ICIs), have significantly increased the efficacy of lung cancer treatment, a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance. Bispecific antibodies (bsAbs) bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles, thus attracting increasing attention as novel antitumor therapies. At present, in addition to the approved bsAb, amivantamab, three novel bsAbs (KN046, AK112, and SHR-1701) are being evaluated in phase 3 clinical trials and many bsAbs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer (NSCLC). Herein we present the structure, classification, and mechanism of action underlying bsAbs in NSCLC and introduce related clinical trials. Finally, we discuss challenges, potential solutions, and future prospects in the context of cancer treatment with bsAbs.

摘要

作为癌症相关死亡的主要原因,肺癌仍然是对人类健康的一个重大威胁。尽管免疫疗法,如免疫检查点抑制剂(ICIs),显著提高了肺癌治疗的疗效,但仍有相当比例的患者对免疫疗法不敏感,且最初对治疗有反应的患者可能很快会产生获得性耐药。双特异性抗体(bsAbs)能同时结合两种不同的抗原或表位,并已显示出在具有合适安全性的情况下增强抗肿瘤疗效,因此作为新型抗肿瘤疗法受到越来越多的关注。目前,除了已获批的双特异性抗体——氨伏单抗外,三种新型双特异性抗体(KN046、AK112和SHR-1701)正在进行3期临床试验评估,许多双特异性抗体正在针对非小细胞肺癌(NSCLC)患者进行1/2期临床试验评估。在此,我们介绍非小细胞肺癌中双特异性抗体的结构、分类及作用机制,并介绍相关临床试验。最后,我们在双特异性抗体癌症治疗的背景下讨论挑战、潜在解决方案和未来前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/edad5c4cdb52/cbm-22-348-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/4460854bfeac/cbm-22-348-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/ac70e04e8de3/cbm-22-348-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/df111a739936/cbm-22-348-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/edad5c4cdb52/cbm-22-348-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/4460854bfeac/cbm-22-348-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/ac70e04e8de3/cbm-22-348-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/df111a739936/cbm-22-348-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d26/12032835/edad5c4cdb52/cbm-22-348-g004.jpg

相似文献

[1]
Application and future prospects of bispecific antibodies in the treatment of non-small cell lung cancer.

Cancer Biol Med. 2025-4-7

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of Exon 20 Insertion-Driven NSCLC.

Cancer Discov. 2020-8

[9]
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[10]
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引用本文的文献

[1]
Emerging IO checkpoints in gastrointestinal oncology.

Front Immunol. 2025-7-24

[2]
Rapid and specific immunoPET imaging of Nectin-4 in gastric cancer and non-small cell lung cancer using [Cu]Cu-NOTA-EV-F(ab').

Eur J Nucl Med Mol Imaging. 2025-6-21

本文引用的文献

[1]
Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions.

Antibodies (Basel). 2024-10-18

[2]
NRG1 Fusions in NSCLC: Being eNRGy Conscious.

Lung Cancer (Auckl). 2024-10-3

[3]
Amivantamab efficacy in wild-type EGFR NSCLC tumors correlates with levels of ligand expression.

NPJ Precis Oncol. 2024-9-6

[4]
Bispecific antibodies: advancing precision oncology.

Trends Cancer. 2024-10

[5]
Ivonescimab: First Approval.

Drugs. 2024-9

[6]
Mechanisms of resistance against T-cell engaging bispecific antibodies in multiple myeloma: implications for novel treatment strategies.

Lancet Haematol. 2024-9

[7]
Site-Specific Antibody Prodrugs via -Arylation: a Bioconjugation Approach Toward Masked Tyrosine Analogues.

J Am Chem Soc. 2024-7-24

[8]
Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial.

Cancer Cell. 2024-7-8

[9]
Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study.

J Clin Oncol. 2024-10-20

[10]
CD74 is associated with inflamed tumor immune microenvironment and predicts responsiveness to PD-1/CTLA-4 bispecific antibody in patients with solid tumors.

Cancer Immunol Immunother. 2024-1-27

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