Adam Kieran, Butler Samuel C, Workman Creg J, Vignali Dario A A
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.
Trends Cancer. 2025 Jan;11(1):37-48. doi: 10.1016/j.trecan.2024.10.009. Epub 2024 Nov 26.
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.
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。
