.special Topic: Fighting Cancer with Armed T Cells an Analytical Biomarker for Treatment of Patients with Recurrent B-all after Remission Induced by Infusion of Anti-cd19 Chimeric Antigen Receptor T (car-t) Cells
.special Topic: Fighting Cancer with Armed T Cells an Analytical Biomarker for Treatment of Patients with Recurrent B-all after Remission Induced by Infusion of Anti-cd19 Chimeric Antigen Receptor T (car-t) Cells
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通讯作者：
Yajing Zhang;Wen-ying Zhang;Hanren Dai;Yao Wang;F. Shi;Chunmeng Wang;Ye-lei Guo;Yang Liu;
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作者：
Yajing Zhang;Wen-ying Zhang;Hanren Dai;Yao Wang;F. Shi;Chunmeng Wang;Ye-lei Guo;Yang Liu;
抗CD 19嵌合抗原受体修饰的T（CART-19）细胞已成为B细胞系急性淋巴细胞白血病的强大靶向免疫疗法，在最近的试验中具有显着的临床反应。尽管如此，关于患者的后续临床监测和治疗的数据很少，特别是那些在CART-19细胞输注后疾病复发的患者。在这里，我们分析了三名在I期临床试验后存活的患者，并通过反映CART-19细胞在体内的持久性的生物标志物和指导进一步治疗的预测因素进行了研究。1例患者获得了9周的持续完全缓解，随后接受了异基因造血干细胞移植。另一名患者在CART-19细胞治疗后20周后表现出复发，在脑脊液中没有检测到白血病，在独立低剂量化疗剂的影响下能够实现形态学缓解。第三名患者在CART-19细胞治疗后的长时间造血缓解期间逐渐发展出广泛的髓外累及组织，其中免疫细胞浸润稀少。在2例患者中发现了血清细胞因子（主要是白细胞介素6和C反应蛋白）的长期和不连续升高（Nos. 1和6），尽管在其外周血中仅可检测到低拷贝数的CAR分子。这一发现表明CART-19细胞的持续功能活性。对挽救治疗前后实验室生物标志物及其临床表现的综合分析表明，对于CART-19诱导缓解后复发的患者，CART-19细胞介导的持续免疫监视将不可避免地增强后续化疗的白血病杀伤效果。（2016年）。一种用于治疗通过输注抗CD 19嵌合抗原受体T（CART）细胞诱导缓解后复发性BALL患者的分析生物标志物。
Anti-CD19 chimeric antigen receptor-modified T (CART -19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CART -19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CART -19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CART -19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemo-therapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune cell infiltration during a long period of hematopoietic remission after CART -19 cell therapy. Long-term and discontin-uous increases in serum cytokines (mainly interleukin 6 and C-reactive protein) were identified in two patients (Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CART -19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CART -19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CART -19-induced remission. (2016). An analytical biomarker for treatment of patients with recurrent BALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CART) cells.