肿瘤细胞治疗研究
英文原题：Emerging immunotherapies in the Hodgkin lymphoma armamentarium.
许多新型免疫疗法在 cHL 中前景广阔。
引言：brentuximab vedotin 和 PD-1 抑制剂改善了经典型霍奇金淋巴瘤（cHL）结局，但对接受这些药物后复发的患者仍需更好的治疗。随着对 cHL 生物学理解加深，多种新疗法正在积极开发。本综述介绍 cHL 新兴免疫治疗药物和联合方案。 综述范围：回顾 FDA 已批准药物以外的新型 PD-1/PD-L1 抑制剂临床试验，靶向 CTLA-4、LAG-3、TIM-3、TIGIT 和 CD47/SIRPα 的检查点抑制剂，PD-1 抑制剂联合免疫调节剂或表观遗传修饰疗法、抗体药物偶联物、双特异性抗体，以及抗 CD30 CAR-T 和异基因 NK 细胞疗法等细胞疗法。本文总结已发表 I/II 期研究的关键安全性和疗效数据，并介绍正在开展的试验，包括首项针对 PD-1 抑制剂耐药 cHL 的 III 期试验。 专家意见：许多新型免疫疗法在 cHL 中展现出很大潜力。与现有药物进行合理联合，并采用新一代抗体和 CAR-T 构建体，可能提高应答率和应答持久性。识别这些免疫疗法的应答生物标志物，并使用循环肿瘤 DNA 等更灵敏工具评估应答，未来或可进一步指导治疗决策并实现精准医疗。
INTRODUCTION: Brentuximab vedotin and PD-1 inhibitors have improved outcomes for classic Hodgkin lymphoma (cHL), but better therapies are needed for patients who relapse after these agents. Based on an improved understanding of cHL biology, there is a robust pipeline of novel therapies in development. In this review, we highlight emerging immunotherapeutic agents and combinations for cHL. AREAS COVERED: We review clinical trials of novel PD-1/PD-L1 inhibitors beyond FDA-approved agents, checkpoint inhibitors targeting CTLA-4, LAG-3, TIM-3, TIGIT, and CD47/SIRP , PD-1 inhibitor combinations with immunomodulatory agents and epigenetic modifying therapies, antibody-drug conjugates, bispecific antibodies, and cellular therapies including anti-CD30 CAR-T and allogeneic NK cell therapy. We review the key safety and efficacy data from published phase 1-2 studies and highlight trials in progress, including the first phase 3 trial for PD-1 inhibitor-refractory cHL. EXPERT OPINION: Many novel immunotherapies hold great promise in cHL. Rational combinations with existing agents and next-generation antibody and CAR-T constructs may improve response rates and durability. Identifying biomarkers of response to these immunotherapies and using more sensitive tools to assess response, such as circulating tumor DNA, may further inform treatment decisions and enable a precision medicine approach in the future.
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