靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Precision targeting of CLDN18.2: A new therapeutic paradigm for gastric cancer.
CLDN18.2 的精准靶向是胃癌治疗中一种有前景的方法,使治疗从传统化疗转向生物标志物指导的策略。
Claudin 18.2(CLDN18.2)是胃癌(GC)中具有吸引力的治疗靶点。靶向CLDN18.2的单克隆抗体zolbetuximab已获批与化疗联用,作为HER2阴性、CLDN18.2阳性胃腺癌患者的一线治疗选择。本综述总结GC中CLDN18.2靶向治疗的当前进展,重点关注单克隆抗体(mAb)的临床开发,尤其是zolbetuximab及新一代抗体,以及基于mAb的联合治疗策略。本文还概述靶向CLDN18.2的抗体药物偶联物(ADC)、双特异性抗体(BsAb)和嵌合抗原受体(CAR)T细胞疗法,并介绍新兴治疗策略。此外,综述还阐述临床及转化研究中的主要挑战和注意事项。总之,精准靶向CLDN18.2代表胃癌治疗中一种有前景的方法,推动治疗从传统化疗转向生物标志物指导的策略。持续开发新一代药物和合理的联合疗法,有望改善治疗结局并扩大获益人群。
Claudin 18.2 (CLDN18.2) is an attractive therapeutic target in gastric cancer (GC). Zolbetuximab, a CLDN18.2-targeted monoclonal antibody, has been approved in combination with chemotherapy as a first-line treatment option for patients with HER2-negative and CLDN18.2-positive gastric adenocarcinoma. This review summarizes current advances in CLDN18.2-targeted therapies for GC, with a focus on the clinical development of monoclonal antibodies (mAbs), particularly zolbetuximab and emerging next-generation antibodies, as well as mAb-based combination strategies. This review also summarizes CLDN18.2-targeted antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor (CAR)-T cell therapy, highlighting emerging therapeutic strategies. Furthermore, major challenges and considerations in clinical and translational research are outlined. In conclusion, precision targeting of CLDN18.2 represents a promising approach in GC therapy, shifting from conventional chemotherapy to biomarker-guided strategies. Continued development of next-generation agents and rational combination therapies may enhance outcomes and expand benefit.
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