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。尽管具有临床疗效，但许多癌症患者对 CAR T 细胞治疗无反应、数月内疾病复发或严重不良事件。此外，在临床试验中，CAR T 细胞疗法在治疗实体瘤方面已显示出极低甚至没有临床疗效。高肿瘤负荷与全身和局部肿瘤微环境之间对 CAR T 细胞疗法临床结果的复杂相互作用正在显现。临床前和临床数据。晚期癌症的标志——即炎症和免疫失调——维持癌症的进展。它们会对 CAR T 细胞产品的生产、扩增、抗肿瘤活性和持久性产生负面影响。了解 CAR T 细胞疗法、其失败的机制以及高肿瘤负荷条件下的不良事件对于充分发挥这种新型治疗方法的潜力至关重要。本综述重点关注将 CAR T 细胞疗法的有效性和安全性联系起来与肿瘤负荷。讨论了其与高肿瘤负荷、全身炎症和免疫失调相关的局限性。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例的新兴临床方法。

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.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.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.