BACKGROUND Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of hematologic malignancies and holds promise for solid tumors. While responses to CAR T-cell therapy have surpassed other available options for patients with refractory malignancies, not all patients respond the same way. The reason for this variability is not currently understood. Therefore, there is a strong need to identify characteristics of patients as well as cellular products that lead to an effective response to CAR T-cell therapy. CONTENT In this review, we discuss potential biomarkers that may predict clinical outcomes of CAR T-cell therapy. Based on correlative findings from clinical trials of both commercially available and early-phase products, we classify biomarkers into categories of pre- and post-infusion as well as patient and product-related markers. Among the biomarkers that have been explored, measures of disease burden both pre- and post-infusion, as well as CAR T-cell persistence post-infusion, are repeatedly identified as predictors of disease response. Higher proportions of early memory T cells at infusion appear to be favorable, and tracking T-cell subsets throughout treatment will likely be critical. SUMMARY There are a growing number of promising biomarkers of CAR T-cell efficacy described in the research setting, however, none of these have been validated for clinical use. Some potentially important predictors of response may be difficult to obtain routinely under the current CAR T-cell therapy workflow. A collaborative approach is needed to select biomarkers that can be validated in large cohorts and incorporated into clinical practice.

中文翻译：

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用于监测嵌合抗原受体 T 细胞治疗的新兴生物标志物

背景嵌合抗原受体（CAR）T细胞疗法彻底改变了血液恶性肿瘤的治疗，并为实体瘤带来了希望。虽然难治性恶性肿瘤患者对 CAR T 细胞疗法的反应超过了其他可用的治疗方案，但并非所有患者的反应都相同。目前尚不清楚这种变化的原因。因此，迫切需要确定患者的特征以及能够对 CAR T 细胞疗法产生有效反应的细胞产品。内容 在这篇综述中，我们讨论了可以预测 CAR T 细胞治疗临床结果的潜在生物标志物。根据市售产品和早期产品临床试验的相关结果，我们将生物标志物分为输注前和输注后以及患者和产品相关标志物类别。在已探索的生物标志物中，输注前和输注后疾病负担的测量以及输注后 CAR T 细胞的持久性被反复确定为疾病反应的预测因子。输注时早期记忆 T 细胞比例较高似乎是有利的，并且在整个治疗过程中跟踪 T 细胞亚群可能至关重要。总结 研究环境中描述了越来越多有前途的 CAR T 细胞功效生物标志物，然而，这些标志物均未经过临床应用验证。在当前的 CAR T 细胞治疗工作流程下，一些潜在的重要反应预测因子可能很难常规获得。需要一种协作方法来选择可以在大型队列中验证并纳入临床实践的生物标志物。