Suppr超能文献

LAG3癌症免疫疗法的进展

Advances in LAG3 cancer immunotherapeutics.

作者信息

Adam Kieran, Butler Samuel C, Workman Creg J, Vignali Dario A A

机构信息

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

出版信息

Trends Cancer. 2025 Jan;11(1):37-48. doi: 10.1016/j.trecan.2024.10.009. Epub 2024 Nov 26.

Abstract

Cancer treatment has entered the age of immunotherapy. Immune checkpoint inhibitor (ICI) therapy has shown robust therapeutic potential in clinical practice, with significant improvements in progression-free survival (PFS) and overall survival (OS). Recently, checkpoint blockade of the lymphocyte activation gene 3 (LAG3) inhibitory receptor (IR) in combination with programmed death protein 1 (PD1) inhibition has been FDA approved in patients with advanced melanoma. This has encouraged the clinical evaluation of new LAG3-directed biologics in combination with other checkpoint inhibitors. Several of these studies are evaluating bispecific antibodies that target exhausted T (T) cells expressing multiple IRs. This review discusses the current understanding of LAG3 in regulating antitumor immunity and the ongoing clinical testing of LAG3 inhibition in cancer.

摘要

癌症治疗已进入免疫疗法时代。免疫检查点抑制剂(ICI)疗法在临床实践中已显示出强大的治疗潜力,无进展生存期(PFS)和总生存期(OS)均有显著改善。最近,淋巴细胞激活基因3(LAG3)抑制性受体(IR)的检查点阻断与程序性死亡蛋白1(PD1)抑制联合应用已获美国食品药品监督管理局(FDA)批准用于晚期黑色素瘤患者。这促使人们对新型LAG3导向生物制剂与其他检查点抑制剂联合应用进行临床评估。其中一些研究正在评估靶向表达多种IR的耗竭性T(T)细胞的双特异性抗体。本综述讨论了目前对LAG3在调节抗肿瘤免疫中的理解以及LAG3抑制在癌症中的正在进行的临床试验。

相似文献

1
Advances in LAG3 cancer immunotherapeutics.
Trends Cancer. 2025 Jan;11(1):37-48. doi: 10.1016/j.trecan.2024.10.009. Epub 2024 Nov 26.
2
Antibodies Against Immune Checkpoint Molecules Restore Functions of Tumor-Infiltrating T Cells in Hepatocellular Carcinomas.
Gastroenterology. 2017 Oct;153(4):1107-1119.e10. doi: 10.1053/j.gastro.2017.06.017. Epub 2017 Jun 23.
4
LAG3 (CD223) as a cancer immunotherapy target.
Immunol Rev. 2017 Mar;276(1):80-96. doi: 10.1111/imr.12519.
6
Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding.
Sci Immunol. 2020 Jul 17;5(49). doi: 10.1126/sciimmunol.abc2728.
7
LAGging behind no more: PD-1 has a new immunotherapy partner.
Immunity. 2024 Oct 8;57(10):2266-2268. doi: 10.1016/j.immuni.2024.09.010.
8
The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment.
Oncologist. 2015 Jul;20(7):812-22. doi: 10.1634/theoncologist.2014-0422. Epub 2015 Jun 11.
9
The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy.
Int Immunopharmacol. 2020 Jan;78:106113. doi: 10.1016/j.intimp.2019.106113. Epub 2019 Dec 13.
10
LAG3 (CD223) and autoimmunity: Emerging evidence.
J Autoimmun. 2020 Aug;112:102504. doi: 10.1016/j.jaut.2020.102504. Epub 2020 Jun 20.

本文引用的文献

1
Structural basis for mouse LAG3 interactions with the MHC class II molecule I-A.
Nat Commun. 2024 Aug 29;15(1):7513. doi: 10.1038/s41467-024-51930-5.
7
Rapid generation of human recombinant monoclonal antibodies from antibody-secreting cells using ferrofluid-based technology.
Front Immunol. 2024 Apr 18;15:1341389. doi: 10.3389/fimmu.2024.1341389. eCollection 2024.
8
The immune checkpoint receptor LAG3: Structure, function, and target for cancer immunotherapy.
J Biol Chem. 2024 May;300(5):107241. doi: 10.1016/j.jbc.2024.107241. Epub 2024 Mar 30.
9
Structural insights reveal interplay between LAG-3 homodimerization, ligand binding, and function.
Proc Natl Acad Sci U S A. 2024 Mar 19;121(12):e2310866121. doi: 10.1073/pnas.2310866121. Epub 2024 Mar 14.
10
T Cell Exhaustion.
Annu Rev Immunol. 2024 Jun;42(1):179-206. doi: 10.1146/annurev-immunol-090222-110914. Epub 2024 Jun 14.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验