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嵌合抗原受体修饰T细胞治疗时代白血病患者微小残留病监测面临的挑战 被引量:5

Challenges of minimal residual disease monitoring in patients with leukemia during chimeric antigen receptor modified T cell immunotherapy
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摘要 嵌合抗原受体(CAR)修饰的T细胞(CAR-T)免疫治疗,在近几年国内外针对难治/复发急性B淋巴细胞白血病(B-ALL)/B细胞淋巴瘤临床研究中疗效惊人,已有两项CAR-T产品经美国FDA批准正式进入临床应用。然而,临床研究也发现CAR-T治疗缓解后,患者总复发率可高达50%以上,其中约20%以上是CAR-T靶向CD分子的阴性复发。靶向分子甚至是原发肿瘤基因异常阴性复发率增加,提示肿瘤细胞在CAR-T高精度靶向治疗压力下,免疫逃逸甚至克隆演变事件发生率迅速上升。监测微小残留病(MRD)以评估疗效、早期发现复发趋势及时指导进一步临床干预,仍是CAR-T治疗时代B-ALL诊断治疗不可或缺的重要辅助手段。而CAR-T治疗后疾病复发的新特点对传统和新兴的MRD检测手段提出了更高的要求,需要进行重新评估和改良以确保CAR-T治疗时代,MRD检测手段依然能够精准有效的评估疗效,监测复发。 Chimeric antigen receptor modified T cell (CAR-T) immunotherapy has achieved remarkable success in the treatment of hematological malignancies, especially for relapsed/refractory acute B lymphocytic leukemia (B-ALL) leukemia patients, most of whom could obtain complete remissions or partial remissions. However, clinical studies also found a as high as 50% total recurrence rate of these patients, in which more than 20% patients relapsed with tumor cells not expressing the primary CAR-T-targeted CD molecules. Increased relapses with negative targeted-molecules or even lost primary abnormal tumor gene, suggesting that immune escape and even clonal evolution events increased rapidly under the high-precision CAR-T immunotherapy pressure. Monitoring of minimal residual disease (MRD) is important to assess the efficacy and find recurrence trends early in a timely manner to guide further clinical intervention. The new features of disease recurrence after CAR-T treatment have put forward higher requirements for traditional and emerging MRD detection methods so as to ensure their effectiveness in the CAR-T treatment era.(Chin J Lab Med, 2018, 41: 175-179)
出处 《中华检验医学杂志》 CAS CSCD 北大核心 2018年第3期175-179,共5页 Chinese Journal of Laboratory Medicine
基金 上海市科学技术委员会医学引导类(西医)科技支撑项目(16411970900) 国家自然科学基金(81470322)
关键词 嵌合抗原受体修饰的T细胞 白血病 微小残留病 Chimeric antigen receptor modified T cell Leukemia Minimal residual disease
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