肿瘤细胞治疗研究
英文原题：Temporal dynamics of substance P and its association with cytokine release syndrome after CD19 CAR-T therapy in pediatric B-ALL.
这些发现提示 SP 动态变化可能与 CRS 期间的早期炎症反应相关，并支持进一步研究 SP-NK1 受体轴作为调节 CD19 CAR-T 相关毒性的潜在治疗靶点。
背景：细胞因子释放综合征（CRS）仍是CAR-T（CAR-T）细胞疗法的一项主要毒性，尤其见于儿童患者。尽管神经免疫介质被认为参与全身炎症，但神经肽P物质（SP）在这一情境中的作用尚未得到研究。 方法：在真实世界临床环境中，18例接受CD19 CAR-T治疗（替沙仑赛）的复发/难治性B细胞急性淋巴细胞白血病（R/R B-ALL）儿童及青年患者，于预设时间点（第−1、+7、+14和+28天）及CRS发生期间（如有额外样本）采集血浆，采用酶联免疫吸附试验（ELISA）测定SP水平并进行纵向分析。研究评估SP动态变化与CRS严重程度、炎症生物标志物及CD19 CAR-T扩增动力学之间的相关性。 结果：发生重度CRS（3级）与非重度CRS的患者基线SP水平相近。相较之下，重度CRS患者SP水平较基线的升幅（ΔSP）显著更高（1523 pg/mL比189 pg/mL，p=0.01）。3例重度CRS患者均在症状起始时出现SP峰值，与临床毒性开始时间吻合，且略早于铁蛋白升高。在这3例患者中，CRS严重程度达到最高时，IL-6水平升高的时间与SP升高接近。总体而言，输注后第+14天SP水平下降，时间上略晚于CAR-T扩增峰值；在发生重度CRS的部分患者中，这一下降与抗CRS治疗给药时间相吻合。观察期末（约第+28天），SP水平随后回升并接近基线。 结论：这些结果提示SP动态变化可能与CRS早期炎症反应有关，支持进一步研究SP-NK1受体轴作为调节CD19 CAR-T相关毒性的潜在治疗靶点。
BACKGROUND: Cytokine Release Syndrome (CRS) remains a major toxicity associated with chimeric antigen receptor T (CAR-T) cell therapy, particularly in pediatric patients. Although neuroimmune mediators have been implicated in systemic inflammation, the role of neuropeptides such as Substance P (SP) in CRS has not yet been explored in this setting. METHODS: Plasma SP levels were measured using an enzyme-linked immunosorbent assay (ELISA) and analyzed longitudinally at predefined time points (day - 1, +7, + 14, and + 28) and during CRS when additional samples were available in 18 pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with CD19 CAR-T therapy (tisagenlecleucel) in a real-world clinical setting. SP dynamics were correlated with severity of CRS, inflammatory biomarkers, and CD19 CAR-T expansion kinetics. RESULTS: Baseline SP levels were similar between patients who developed severe CRS (grade 3) and those with non-severe CRS. In contrast, the increase in SP levels from baseline ( SP) was significantly higher in patients who developed severe CRS (1523 pg/mL vs. 189 pg/mL, p = 0.01). A peak in SP levels was observed at the onset of severe CRS in all three patients, coinciding with the beginning of clinical toxicity and occurring shortly before the elevation in ferritin levels. In these three cases, IL-6 levels increased in close temporal proximity to the rise in SP at the time of maximum CRS severity. Overall, SP levels declined by day + 14 post-infusion, shortly after the peak of CAR-T expansion. This decline coincided temporally with the administration of anti-CRS treatment in the subset of patients with severe CRS. SP levels later increased toward the end of the observation period (around day + 28), approaching baseline values. CONCLUSIONS: These findings suggest that SP dynamics may be linked to the early inflammatory response during CRS and support further investigation of the SP-NK1 receptor axis as a potential therapeutic target to modulate CD19 CAR-T-related toxicity.
MEMBER ACCOUNT
登录成功会直接打开下一页。
