Morchón-Araujo Daniel, Catani Greta, Mirallas Oriol, Pretelli Giulia, Sánchez-Pérez Vicky, Vieito María, Braña Irene, Pujol-Borrell Ricardo, Garralda Elena, Hernando-Calvo Alberto
Department of Medical Oncology, University Hospital of Salamanca, IBSAL, 37007 Salamanca, Spain.
Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
Int J Mol Sci. 2025 Jun 4;26(11):5394. doi: 10.3390/ijms26115394.
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.
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。