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体内抗体文库筛选鉴定出靶向PKM2的M1抗体,其在黑色素瘤中具有抗肿瘤活性。

In vivo antibody library screening identifies PKM2-targeting M1 antibody with antitumor activity in melanoma.

作者信息

In Hyukmin, Choi Yong Hwan, Kang Sunghyun, Han Kyung Ho

机构信息

Department of Biological Sciences and Biotechnology, Hannam University Daejeon 34054, South Korea.

Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon 34141, South Korea.

出版信息

Am J Cancer Res. 2025 Aug 15;15(8):3460-3470. doi: 10.62347/PSJY2877. eCollection 2025.

DOI:10.62347/PSJY2877
PMID:40948527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12432578/
Abstract

In this study, we introduce an innovative in vivo antibody screening method to identify antibodies that can inhibit melanoma cell growth and induce apoptosis. By using a lentiviral ScFv library, we developed a platform that allows for the direct suppression of melanoma cell proliferation within a living mouse model. Through this approach, we identified the M1 antibody, which targets PKM2, a key protein involved in tumor progression. The M1 antibody was found to significantly inhibit melanoma cell growth by disrupting the function of PKM2. Although PKM2 is widely recognized as an important factor in various cancers, no commercial therapeutic agents currently target this protein. Our findings indicate that the in vivo antibody screening method is a reliable and effective approach for isolating antibodies for melanoma therapy. Moreover, the M1 antibody shows great potential as a promising candidate for developing novel treatments for human melanoma.

摘要

在本研究中,我们引入了一种创新的体内抗体筛选方法,以鉴定能够抑制黑色素瘤细胞生长并诱导凋亡的抗体。通过使用慢病毒单链抗体库,我们开发了一个平台,该平台能够在活体小鼠模型中直接抑制黑色素瘤细胞增殖。通过这种方法,我们鉴定出了靶向PKM2的M1抗体,PKM2是一种参与肿瘤进展的关键蛋白。发现M1抗体通过破坏PKM2的功能来显著抑制黑色素瘤细胞生长。尽管PKM2被广泛认为是各种癌症中的一个重要因素,但目前尚无商业治疗药物靶向该蛋白。我们的研究结果表明,体内抗体筛选方法是分离用于黑色素瘤治疗的抗体的可靠且有效的方法。此外,M1抗体作为开发人类黑色素瘤新疗法的有前景的候选药物具有巨大潜力。

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本文引用的文献

1
Cutaneous melanoma.皮肤黑素瘤。
Lancet. 2023 Aug 5;402(10400):485-502. doi: 10.1016/S0140-6736(23)00821-8. Epub 2023 Jul 24.
2
Agonist (P1) Antibody Converts Stem Cells into Migrating Beta-Like Cells in Pancreatic Islets.激动剂(P1)抗体将干细胞转化为胰岛中迁移的类似β细胞。
J Microbiol Biotechnol. 2022 Dec 28;32(12):1615-1621. doi: 10.4014/jmb.2209.09031. Epub 2022 Oct 28.
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Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications.结直肠癌中的瓦博格效应:在肿瘤微环境中的新兴作用及其治疗意义。
J Hematol Oncol. 2022 Nov 1;15(1):160. doi: 10.1186/s13045-022-01358-5.
4
Phage Display: A promising selection strategy for the improvement of antibody targeting and drug delivery properties.噬菌体展示:一种用于改善抗体靶向性和药物递送特性的有前景的筛选策略。
Front Microbiol. 2022 Sep 26;13:962124. doi: 10.3389/fmicb.2022.962124. eCollection 2022.
5
Antibodies Regulate Dual-Function Enzyme IYD to Induce Functional Synergy between Metabolism and Thermogenesis.抗体调节双功能酶 IYD 以诱导代谢和产热之间的功能协同作用。
Int J Mol Sci. 2022 Jul 15;23(14):7834. doi: 10.3390/ijms23147834.
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Inhibition of PKM2 Enhances Sensitivity of Olaparib to Ovarian Cancer Cells and Induces DNA Damage.PKM2 抑制增强奥拉帕利对卵巢癌细胞的敏感性并诱导 DNA 损伤。
Int J Biol Sci. 2022 Jan 24;18(4):1555-1568. doi: 10.7150/ijbs.62947. eCollection 2022.
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Extracellular PKM2 facilitates organ-tissue fibrosis progression.细胞外丙酮酸激酶M2促进器官组织纤维化进展。
iScience. 2021 Sep 25;24(10):103165. doi: 10.1016/j.isci.2021.103165. eCollection 2021 Oct 22.
8
Antibody Libraries as Tools to Discover Functional Antibodies and Receptor Pleiotropism.抗体文库作为发现功能性抗体和受体多效性的工具。
Int J Mol Sci. 2021 Apr 16;22(8):4123. doi: 10.3390/ijms22084123.
9
Pyruvate kinase M2 (PKM2) in cancer and cancer therapeutics.丙酮酸激酶 M2(PKM2)在癌症和癌症治疗中的作用。
Cancer Lett. 2021 Apr 10;503:240-248. doi: 10.1016/j.canlet.2020.11.018. Epub 2020 Nov 24.
10
Efficacy and mechanism of combination of oxaliplatin with PKM2 knockdown in colorectal cancer.奥沙利铂与PKM2基因敲低联合应用于结直肠癌的疗效及机制
Oncol Lett. 2020 Dec;20(6):312. doi: 10.3892/ol.2020.12175. Epub 2020 Sep 30.