肿瘤细胞治疗研究
英文原题：Claudin 18.2 as a novel therapeutic target.
Claudin 18.2 as a novel therapeutic target.
Claudin 18.2 是一种主要存在于非恶性胃上皮中的紧密连接分子，在恶性转化过程中可在肿瘤细胞表面被接触，从而为癌症治疗提供了一个有吸引力的靶点。
Claudin 18.2是一种主要存在于非恶性胃上皮的紧密连接分子，在恶性转化过程中可在肿瘤细胞表面被暴露，从而成为一个有吸引力的癌症治疗靶点。两项测试抗claudin 18.2抗体zolbetuximab的III期试验数据已确立，claudin 18.2阳性晚期胃癌是一个独立的治疗亚群，可从化疗基础上加用该药物中获益。这一进展大幅提高了符合靶向治疗条件的患者比例。此外，高亲和力单克隆抗体、双特异性抗体、CAR-T 细胞以及具有旁观者杀伤效应的抗体-药物偶联物等较新疗法，在表达claudin 18.2的胃癌患者中显示出相当大的前景。这一新进展源于药物开发者超越了传统靶点，如驱动基因改变或生长因子。在本综述中，我们强调其生物学依据，并探讨靶向claudin 18.2的疗法在晚期胃癌患者中的临床活性，同时探索将claudin 18.2靶向疗法扩展至其他claudin 18.2阳性实体瘤患者的潜力。
Claudin 18.2, a tight-junction molecule predominantly found in the nonmalignant gastric epithelium, becomes accessible on the tumour cell surface during malignant transformation, thereby providing an appealing target for cancer therapy. Data from two phase III trials testing the anti-claudin 18.2 antibody zolbetuximab have established claudin 18.2-positive advanced-stage gastric cancers as an independent therapeutic subset that derives benefit from the addition of this agent to chemotherapy. This development has substantially increased the percentage of patients eligible for targeted therapy. Furthermore, newer treatments, such as high-affinity monoclonal antibodies, bispecific antibodies, chimeric antigen receptor T cells and antibody-drug conjugates capable of bystander killing effects, have shown considerable promise in patients with claudin 18.2-expressing gastric cancers. This new development has resulted from drug developers moving beyond traditional targets, such as driver gene alterations or growth factors. In this Review, we highlight the biological rationale and explore the clinical activity of therapies that target claudin 18.2 in patients with advanced-stage gastric cancer and explore the potential for expansion of claudin 18.2-targeted therapies to patients with other claudin 18.2-positive solid tumours.
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