Abstract：
UNASSIGNED: Chimeric antigen receptor (CAR) T-cell therapy has redefined the therapeutic landscape of several hematologic malignant tumors. Despite its clinical efficacy, many patients with cancer experience nonresponse to CAR T-cell treatment, disease relapse within months, or severe adverse events. Furthermore, CAR T-cell therapy has demonstrated minimal to no clinical efficacy in the treatment of solid tumors in clinical trials.
UNASSIGNED: A complex interplay between high tumor burden and the systemic and local tumor microenvironment on clinical outcomes of CAR T-cell therapy is emerging from preclinical and clinical data. The hallmarks of advanced cancers-namely, inflammation and immune dysregulation-sustain cancer progression. They negatively affect the production, expansion, antitumor activity, and persistence of CAR T-cell products. Understanding of CAR T-cell therapy, mechanisms underlying its failure, and adverse events under conditions of high tumor burden is critical for realizing the full potential of this novel treatment approach.
UNASSIGNED: This review focuses on linking the efficacy and safety of CAR T-cell therapy with tumor burden. Its limitations relative to high tumor burden, systemic inflammation, and immune dysregulation are discussed. Emerging clinical approaches to overcome these obstacles and more effectively incorporate this therapeutic strategy into the treatment paradigm of patients with solid malignant tumors are also described.
UNASSIGNED: A complex interplay between high tumor burden and the systemic and local tumor microenvironment on clinical outcomes of CAR T-cell therapy is emerging from preclinical and clinical data. The hallmarks of advanced cancers-namely, inflammation and immune dysregulation-sustain cancer progression. They negatively affect the production, expansion, antitumor activity, and persistence of CAR T-cell products. Understanding of CAR T-cell therapy, mechanisms underlying its failure, and adverse events under conditions of high tumor burden is critical for realizing the full potential of this novel treatment approach.
UNASSIGNED: This review focuses on linking the efficacy and safety of CAR T-cell therapy with tumor burden. Its limitations relative to high tumor burden, systemic inflammation, and immune dysregulation are discussed. Emerging clinical approaches to overcome these obstacles and more effectively incorporate this therapeutic strategy into the treatment paradigm of patients with solid malignant tumors are also described.
摘要：
■嵌合抗原受体（CAR）T细胞疗法重新定义了几种血液恶性肿瘤的治疗前景。尽管它的临床疗效，许多癌症患者对CAR-T细胞治疗没有反应，疾病在几个月内复发，或严重不良事件。此外，在临床试验中，CAR-T细胞疗法在实体瘤的治疗中表现出最小甚至没有临床疗效。
■高肿瘤负荷与全身和局部肿瘤微环境对CAR-T细胞治疗临床结果的复杂相互作用正在从临床前和临床数据中显现出来。晚期癌症的标志——即，炎症和免疫失调维持癌症进展。它们对生产产生负面影响，扩展,抗肿瘤活性，以及CAR-T细胞产品的持久性。了解CAR-T细胞疗法，其失败背后的机制，高肿瘤负荷条件下的不良事件对于实现这种新型治疗方法的全部潜力至关重要。
■这篇综述的重点是将CAR-T细胞疗法的疗效和安全性与肿瘤负荷联系起来。其局限性相对于高肿瘤负荷，全身性炎症,并讨论了免疫失调。还描述了克服这些障碍并更有效地将这种治疗策略纳入实体恶性肿瘤患者的治疗范式的新兴临床方法。
■高肿瘤负荷与全身和局部肿瘤微环境对CAR-T细胞治疗临床结果的复杂相互作用正在从临床前和临床数据中显现出来。晚期癌症的标志——即，炎症和免疫失调维持癌症进展。它们对生产产生负面影响，扩展,抗肿瘤活性，以及CAR-T细胞产品的持久性。了解CAR-T细胞疗法，其失败背后的机制，高肿瘤负荷条件下的不良事件对于实现这种新型治疗方法的全部潜力至关重要。
■这篇综述的重点是将CAR-T细胞疗法的疗效和安全性与肿瘤负荷联系起来。其局限性相对于高肿瘤负荷，全身性炎症,并讨论了免疫失调。还描述了克服这些障碍并更有效地将这种治疗策略纳入实体恶性肿瘤患者的治疗范式的新兴临床方法。
