Du Mengyi, Hari Parameswaran, Hu Yu, Mei Heng
1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China.
2Division of Hematology/Oncology, Medical College of Wisconsin (MCW), Milwaukee, WI USA.
Biomark Res. 2020 May 11;8:13. doi: 10.1186/s40364-020-00190-8. eCollection 2020.
The development of chimeric antigen receptor (CAR) T cell immunotherapy has achieved promising results, both in clinical studies and in commercial products for patients with hematologic malignancies. Despite high remission rates of CAR-T cell therapy in previously untreatable, refractory and/or relapsed patients, several challenges in CAR-T therapy remain to be overcome, especially in integrating such therapies into personalized disease management approaches. Given the unique characteristics of CAR-T therapy, it is particularly urgent to identify biomarkers to maximize their clinical benefits. This systematic review summarizes clinically relevant biomarkers that may help individualized disease management in patients receiving CAR-T cell therapy in terms of toxicity warning, efficacy prediction and relapse monitoring. We summarize data from 18 clinical trials, including traditional indicators like cytokines, biochemical proteins, tumor burden, as well as potential novel indicators such as CAR-T cell expansion and persistency. The establishment of a biomarker-based system aimed at individualized management is recommended to guide better clinical application of CAR-T products.
嵌合抗原受体(CAR)T细胞免疫疗法的发展在血液系统恶性肿瘤患者的临床研究和商业产品方面均取得了令人瞩目的成果。尽管CAR-T细胞疗法在既往无法治疗、难治性和/或复发性患者中具有较高的缓解率,但CAR-T疗法仍面临一些挑战有待克服,尤其是将此类疗法纳入个性化疾病管理方法中。鉴于CAR-T疗法的独特特性,识别生物标志物以最大化其临床益处尤为迫切。本系统综述总结了临床相关生物标志物,这些生物标志物在毒性预警、疗效预测和复发监测方面可能有助于接受CAR-T细胞疗法患者的个性化疾病管理。我们总结了18项临床试验的数据,包括细胞因子、生化蛋白、肿瘤负荷等传统指标,以及CAR-T细胞扩增和持久性等潜在新指标。建议建立基于生物标志物的个体化管理系统,以指导CAR-T产品更好地临床应用。