CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytokine release syndrome in solid tumors.
Cytokine release syndrome in solid tumors.
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CRS 是癌症免疫治疗常见且可能严重的并发症,相关疗法包括 CAR-T、双特异性 T 细胞衔接器,较少见于免疫检查点抑制剂。尽管大量研究已为血液系统恶性肿瘤 CRS 管理制定指南,但由于肿瘤微环境、免疫治疗适应证和患者人群存在差异,实体器官肿瘤 CRS 管理日益需要专门关注。本综述概述实体瘤 CRS,包括其病理生理学、临床表现和现行管理策略。实体瘤 CRS 的复杂性源于肿瘤微环境的免疫抑制特性,以及肿瘤相关抗原与健康组织抗原重叠,这可能增加严重靶向肿瘤外毒性风险。综述强调,早期识别和分级 CRS 对患者安全和有效干预至关重要。轻症 CRS 采用支持治疗;严重病例通常需 tocilizumab、皮质类固醇等靶向治疗,必要时转入重症监护病房提供器官支持。是否再次挑战免疫治疗或暂停治疗,需仔细权衡患者个体目标和风险。其他细胞因子抑制剂、血浆置换及自杀基因系统等新兴疗法,是减轻严重 CRS 的潜在途径。未来研究聚焦优化风险分层工具、开发新疗法和评估长期结局。深入理解实体瘤 CRS 将有助于制定更个体化的治疗方法,提高该患者群体免疫疗法的安全性和疗效。
Cytokine release syndrome (CRS) is a common and potentially severe complication of cancer immunotherapy, including CAR T-cell therapies, bispecific T-cell engagers, and less commonly immune checkpoint inhibitors. Although extensive research has established guidelines for managing CRS in hematological malignancies, there is a growing need to address CRS in the context of solid organ tumors due to differences in tumor microenvironment, immunotherapy indications, and patient population. This review aims to provide an overview of CRS in solid tumors, outlining its pathophysiology, clinical presentation, and current management strategies. The complexities of CRS in solid tumors arise from challenges such as the immunosuppressive nature of the tumor microenvironment and the overlap of tumor-associated antigens with healthy tissues, potentially increasing the risk of severe on-target off-tumor toxicities.
The review emphasizes early detection and grading of CRS as essential for patient safety and effective intervention. Management of CRS involves supportive care for mild cases, whereas severe presentations often require targeted therapies like tocilizumab, corticosteroids, and escalation to the intensive care unit for organ support. The decision to rechallenge or withhold immunotherapy requires careful consideration of patient-specific goals and risks.
Emerging treatments such as other cytokine inhibitors, plasma exchange, and suicide gene systems are promising avenues for mitigating severe CRS. Future research focuses on refining risk stratification tools, novel therapeutic agents, and evaluating long-term outcomes. A deeper understanding of CRS in solid tumors will enable more personalized treatment approaches, enhancing the safety and efficacy of immunotherapies for this patient population.
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