肿瘤细胞治疗研究
英文原题：Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy.
43例初始缓解患者的四种MM EV亚群均显著减少，而19例进展患者的BCMA+、GPRC5D+和CD319+ MM EV增加，并通过BCMA+ MM EV检测到抗原逃逸。
细胞外囊泡（EVs）在多发性骨髓瘤（MM）中代表了一种有前景的液体活检平台。我们开发了一种MM EV表面蛋白检测方法，用于在45例接受抗BCMA嵌合抗原受体（CAR）T细胞治疗的复发/难治性MM（RRMM）患者的336份连续血液样本中，对由可靶向MM表面蛋白（BCMA、CD38、GPRC5D和CD319）定义的四个MM EV亚群进行定量和动态监测。在43例初始应答患者中，所有四个MM EV亚群均显著下降，而在19例疾病进展患者中，BCMA+、GPRC5D+和CD319+ MM EVs升高，并且通过BCMA+ MM EVs检测到抗原逃逸。MM EV亚群可区分微小残留病（MRD）状态，并补充MRD以在临床进展前检测早期复发。值得注意的是，CD319+ MM EVs是MRD阴性患者无进展生存期和总生存期的早期预测因子。该检测方法能够无创监测深度应答、疾病进展和抗原逃逸，并对MRD阴性RRMM患者进行生存分层。
Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA + , GPRC5D + , and CD319 + MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA + MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319 + MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.
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