Emerging Biomarkers for Monitoring Chimeric Antigen Receptor T-Cell Therapy

嵌合抗原受体 医学 细胞疗法 临床试验 疾病 汽车T细胞治疗 免疫疗法 T细胞 疾病监测 肿瘤科 细胞 免疫学 内科学 免疫系统 生物 遗传学
作者
Tewodros Mamo,Alexandra Dreyzin,David F. Stroncek,David H. McKenna
出处
期刊:Clinical Chemistry [Oxford University Press]
卷期号:70 (1): 116-127 被引量:1
标识
DOI:10.1093/clinchem/hvad179
摘要

Abstract 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.
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