Maali Amirhosein, Noei Ahmad, Feghhi-Najafabadi Saba, Sharifzadeh Zahra
Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Student Research Committee, Pasteur Institute of Iran, Tehran, Iran.
Iran Biomed J. 2024 Sep 1;28(5 & 6):221-34. doi: 10.61186/ibj.4444.
Chimeric antigen receptor T-cell therapy is a groundbreaking approach for treating certain hematologic malignancies and solid tumors. However, its application is limited by severe toxicities, particularly CRS and ICANS, dramatically limit its broader application. IL-1 plays a crucial role in both enhancing CAR T-cell efficacy and driving these toxic effects. This review systematically examines the dual functions of IL-1, highlighting its role in promoting CAR T-cell activation and persistence while contributing to CRS and ICANS pathogenesis. Strategies to mitigate IL-1-driven toxicities, including IL-1 receptor antagonists, monoclonal antibodies, IL-1 trapping, and interference with IL-1 production, show promise in reducing adverse effects without compromising therapeutic efficacy. Understanding the complex role of IL-1 in CAR T-cell therapy may lead to optimized treatment strategies, improving safety and expanding clinical applicability. Further research is essential to refine IL-1-targeted interventions and enhance the therapeutic potential of CAR T-cell therapy. Chimeric antigen receptor (CAR) T-cell therapy is a groundbreaking approach for treating certain hematologic malignancies and solid tumors. However, its application is limited by severe toxicities, particularly cytokine release syndrome (CRS) and cell-associated neurotoxicity syndrome (ICANS), dramatically limit its broader application. IL-1 plays a crucial role in both enhancing CAR T-cell efficacy and driving these toxic effects. This review systematically examines the dual functions of IL-1, highlighting its role in promoting CAR T-cell activation and persistence while contributing to CRS and ICANS pathogenesis. Strategies to mitigate IL-1-driven toxicities, including IL-1 receptor antagonists, monoclonal antibodies, IL-1 trapping, and interference with IL-1 production, show promise in reducing adverse effects without compromising therapeutic efficacy. Understanding the complex role of IL-1 in CAR T-cell therapy may lead to optimized treatment strategies, improving safety and expanding clinical applicability. Further research is essential to refine IL-1-targeted interventions and enhance the therapeutic potential of CAR T-cell therapy.
嵌合抗原受体T细胞疗法是治疗某些血液系统恶性肿瘤和实体瘤的开创性方法。然而，其应用受到严重毒性的限制，尤其是细胞因子释放综合征（CRS）和与细胞相关的神经毒性综合征（ICANS），这极大地限制了其更广泛的应用。白细胞介素-1（IL-1）在增强嵌合抗原受体T细胞疗效和引发这些毒性作用方面都起着关键作用。本综述系统地研究了IL-1的双重功能，突出了其在促进嵌合抗原受体T细胞活化和持久性方面的作用，同时也参与了CRS和ICANS的发病机制。减轻IL-1驱动毒性的策略，包括IL-1受体拮抗剂、单克隆抗体、IL-1捕获以及干扰IL-1的产生，有望在不影响治疗效果的情况下减少不良反应。了解IL-1在嵌合抗原受体T细胞疗法中的复杂作用可能会带来优化的治疗策略，提高安全性并扩大临床适用性。进一步的研究对于完善以IL-1为靶点的干预措施和增强嵌合抗原受体T细胞疗法的治疗潜力至关重要。嵌合抗原受体（CAR）T细胞疗法是治疗某些血液系统恶性肿瘤和实体瘤的开创性方法。然而，其应用受到严重毒性的限制，尤其是细胞因子释放综合征（CRS）和与细胞相关的神经毒性综合征（ICANS），这极大地限制了其更广泛的应用。白细胞介素-1（IL-1）在增强嵌合抗原受体T细胞疗效和引发这些毒性作用方面都起着关键作用。本综述系统地研究了IL-1的双重功能，突出了其在促进嵌合抗原受体T细胞活化和持久性方面的作用，同时也参与了CRS和ICANS的发病机制。减轻IL-1驱动毒性的策略，包括IL-1受体拮抗剂、单克隆抗体、IL-1捕获以及干扰IL-1的产生，有望在不影响治疗效果的情况下减少不良反应。了解IL-1在嵌合抗原受体T细胞疗法中的复杂作用可能会带来优化的治疗策略，提高安全性并扩大临床适用性。进一步的研究对于完善以IL-1为靶点的干预措施和增强嵌合抗原受体T细胞疗法的治疗潜力至关重要。
