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靶向 Claudin-18.2 的癌症治疗:2024 ASCO 年会更新

英文原题:Targeting Claudin-18.2 for cancer therapy: updates from 2024 ASCO annual meeting.

PubMed 2024/08/26(内容时间) J Hematol Oncol Q1 · IF 47.8(JCR 2025)

研究概要

针对claudin-18亚型2(CLDN18.2)的多类疗法正在开发中,用于治疗晚期胃食管腺癌和其他实体瘤。

中文摘要

针对claudin-18异构体2(CLDN18.2)的多类疗法正在开发中,用于治疗晚期胃食管腺癌和其他实体瘤。在2024年美国临床肿瘤学会(ASCO)年会上,公布了3期SPOTLIGHT试验的最终结果,证明在CLDN18.2表达≥ 75%的晚期胃食管腺癌一线治疗中,将CLDN18.2特异性抗体zolbetuximab加入化疗可带来显著的生存获益。在ASCO 2024上公布的早期试验结果显示,去岩藻糖基化CLDN18.2特异性抗体FG-M108联合化疗在CLDN18.2阳性晚期胃食管癌和胰腺癌一线治疗中具有良好的疗效和安全性。此外,在ASCO 2024上公布的几项早期试验研究了其他针对CLDN18.2的方法在CLDN18.2阳性难治性晚期实体瘤中的应用,包括靶向CLDN18.2的抗体药物偶联物LM-302和IBI343、双特异性抗CLDN18.2/CD3抗体IBI38,以及CAR-T 细胞疗法satricabtagene autoleucel。这些新方法可能有望将CLDN18.2靶向疗法的获益扩展至更广泛的肿瘤类型以及表达较低水平CLDN18.2的肿瘤。

展开英文摘要原文

Multiple classes of therapies targeting claudin-18 isoform 2 (CLDN18.2) are under development for the treatment of advanced gastroesophageal adenocarcinoma and other solid tumors. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression. Early-phase trial results presented at ASCO 2024 showed promising efficacy and safety of the afucosylated CLDN18.2-specific antibody FG-M108 in combination with chemotherapy in the first-line treatment of CLDN18.2-positive advanced gastroesophageal and pancreatic cancers. In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody-drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2.

论文信息

作者
Zhou KI、Strickler JH、Chen H
第一作者单位
Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, 27708, Durham, NC, USA.United States
通讯作者单位
Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, 27708, Durham, NC, USA. hui.chen@duke.edu.United States
文献类型
读者来信
期刊
Journal of hematology & oncology2024 Aug 26
原文标识
PubMed 39183320 · DOI 10.1186/s13045-024-01595-w