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早期药物研发中新兴的免疫治疗靶点

Emerging Immunotherapy Targets in Early Drug Development.

作者信息

Morchón-Araujo Daniel, Catani Greta, Mirallas Oriol, Pretelli Giulia, Sánchez-Pérez Vicky, Vieito María, Braña Irene, Pujol-Borrell Ricardo, Garralda Elena, Hernando-Calvo Alberto

机构信息

Department of Medical Oncology, University Hospital of Salamanca, IBSAL, 37007 Salamanca, Spain.

Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.

出版信息

Int J Mol Sci. 2025 Jun 4;26(11):5394. doi: 10.3390/ijms26115394.

Abstract

Immunotherapy has significantly changed the treatment paradigm for solid tumors, with immune checkpoint inhibitors now established in the management of many malignancies. Despite initial success, durable responses remain limited to a subset of patients, often less than 30%, due to both intrinsic and acquired resistance mechanisms. These challenges have prompted the development of next-generation immunotherapies. Recent efforts have expanded the scope of immunotherapy beyond PD-1/PD-L1 and CTLA-4 inhibition, focusing on new immune targets currently under investigation in early phase clinical trials. These include novel immune checkpoint inhibitors, immunomodulators targeting the tumor microenvironment, and bispecific antibodies. This review provides a comprehensive overview of emerging immune targets currently being investigated in early drug development, discussing their mechanisms of action, preliminary clinical outcomes, and potential future directions.

摘要

免疫疗法显著改变了实体瘤的治疗模式,免疫检查点抑制剂现已在多种恶性肿瘤的治疗中确立了地位。尽管取得了初步成功,但由于内在和获得性耐药机制,持久反应仍仅限于一部分患者,通常不到30%。这些挑战促使了下一代免疫疗法的发展。最近的努力将免疫疗法的范围扩展到了PD-1/PD-L1和CTLA-4抑制之外,重点关注目前正在早期临床试验中研究的新免疫靶点。这些包括新型免疫检查点抑制剂、靶向肿瘤微环境的免疫调节剂和双特异性抗体。本综述全面概述了目前在早期药物开发中正在研究的新兴免疫靶点,讨论了它们的作用机制、初步临床结果和潜在的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f82/12155519/6cbcf0a503df/ijms-26-05394-g001.jpg

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