横向研究了B细胞恶性肿瘤的CD19-CAR-T细胞治疗的血清蛋白组学特征化。
Longitudinal Serum Proteomics Characterization of CD19-CAR-T Cell Therapy for B-Cell Malignancies.
发表日期：2023 Aug 02
作者：
Youming Wang, Rui Sun, Weigang Ge, Lei Xue, Qianwen Xu, Hui Xu, Sujun Li, Miaomiao Wu, Tiannan Guo, Xingbing Wang
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
嵌合抗原受体（CAR）修饰的T细胞在治疗B细胞白血病方面表现出明显的疗效。然而，经过治疗的患者可能会出现副作用，例如细胞因子释放综合征（CRS），其中机制尚不清楚。在这里，我们收集了来自8例B细胞急性淋巴细胞性白血病（B-ALL）患者的43份血清样本，分别在CD19特异性CAR-T细胞治疗前和5个时间点后进行。使用TMTpro 16-plex基于定量蛋白组学，我们定量了1151个蛋白质，并对每个患者的纵向蛋白质组分析进行了概述。治疗后7天，我们发现了最严重的炎性蛋白质失调。脂质代谢蛋白质，包括APOA1，在治疗后减少，7天后达到最低点，然后逐渐恢复。因此，APOA1已被选为CRS疾病进展的潜在生物标志物。此外，我们确定了CD163作为CRS严重程度的潜在生物标志物。这两个生物标志物在一个独立队列中成功进行了有针对性蛋白质组学验证。我们的研究为CAR-T细胞治疗引起的CRS提供了新的见解。我们所确定的生物标志物可能有助于开发有针对性的药物和监测策略。
Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable efficacy in treating B-cell leukemia. However, treated patients may potentially develop side effects, such as cytokine release syndrome (CRS), the mechanisms of which remain unclear. Here, we collected 43 serum samples from eight patients with B-cell acute lymphoblastic leukemia (B-ALL) before and five time points after CD19-specific CAR-T cell treatment. Using TMTpro 16-plex-based quantitative proteomics, we quantified 1151 proteins and profiled the longitudinal proteomes analysis of each patient. Seven days after therapy, we found the most dysregulated inflammatory proteins. Lipid metabolism proteins, including APOA1, decreased after therapy, reached their minimum after 7 days, and then gradually recovered. Hence, APOA1 has been selected as a potential biomarker of the CRS disease progression. Furthermore, we identified CD163 as a potential biomarker of CRS severity. These two biomarkers were successfully validated using targeted proteomics in an independent cohort. Our study provides new insights into CAR-T cell therapy-induced CRS. The biomarkers we identified may help develop targeted drugs and monitoring strategies.