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CD44v6、STn 与 O-GD2:为新型肿瘤靶向治疗铺路的有前景肿瘤相关抗原

英文原题:CD44v6, STn & O-GD2: promising tumor associated antigens paving the way for new targeted cancer therapies.

PubMed 2023/10/03(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

靶向治疗是当今肿瘤学的最先进手段,每年都有新的肿瘤相关抗原(TAA)被开发用于临床前研究和临床试验,但其中真正改变治疗格局的很少。

中文摘要

靶向治疗是当前肿瘤学的重要方向,每年都有新的肿瘤相关抗原(TAA)进入临床前研究和临床试验,但真正改变治疗格局的靶点仍很少。主要瓶颈包括难以找到仅在肿瘤中表达的抗原,以及难以制备针对这些抗原的高质量结合分子。差异性剪接和糖基化等特殊细胞机制可产生新抗原。与因mRNA加工增强而导致抗原表达量升高或降低不同,这些过程的改变可产生本质异常的细胞表面蛋白,因此能提供更特异的靶点以实现精准抗肿瘤治疗。本文介绍几种有潜力的TAA,可用于癌症监测、靶向治疗及新型免疫治疗工具开发,如重组抗体、嵌合抗原受体(CAR)T细胞和CAR工程化NK细胞,以特异性杀伤多种肿瘤。综述重点更新CD44v6、STn和O-GD2等TAA,介绍其来源,以及它们作为多种肿瘤疾病生物标志物和治疗靶点的当前与潜在用途。

展开英文摘要原文

Targeted therapies are the state of the art in oncology today, and every year new Tumor-associated antigens (TAAs) are developed for preclinical research and clinical trials, but few of them really change the therapeutic scenario. Difficulties, either to find antigens that are solely expressed in tumors or the generation of good binders to these antigens, represent a major bottleneck. Specialized cellular mechanisms, such as differential splicing and glycosylation processes, are a good source of neo-antigen expression. Changes in these processes generate surface proteins that, instead of showing decreased or increased antigen expression driven by enhanced mRNA processing, are aberrant in nature and therefore more specific targets to elicit a precise anti-tumor therapy. Here, we present promising TAAs demonstrated to be potential targets for cancer monitoring, targeted therapy and the generation of new immunotherapy tools, such as recombinant antibodies and chimeric antigen receptor (CAR) T cell (CAR-T) or Chimeric Antigen Receptor-Engineered Natural Killer (CAR-NK) for specific tumor killing, in a wide variety of tumor types. Specifically, this review is a detailed update on TAAs CD44v6, STn and O-GD2, describing their origin as well as their current and potential use as disease biomarker and therapeutic target in a diversity of tumor types.

论文信息

作者
Lodewijk I、Dueñas M、Paramio JM、Rubio C
单位
Biomedical Research Institute I+12, University Hospital "12 de Octubre", Madrid, Spain.Spain
文献类型
非美国政府资助研究 · 综述
期刊
Frontiers in immunology2023
原文标识
PubMed 37854601 · DOI 10.3389/fimmu.2023.1272681