Study on the Prognostic Value of Aberrant Antigen in Patients With Acute B Lymphocytic Leukemia
Study on the Prognostic Value of Aberrant Antigen in Patients With Acute B Lymphocytic Leukemia
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DOI：
10.1016/j.clml.2019.03.012
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发表时间：
2019-07-01
影响因子：
2.7
通讯作者：
Zhang, Cheng
中科院分区：
文献类型：
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作者：
Liu, Jun;Tan, Xu;Zhang, Cheng
嵌合抗原受体重定向T细胞（CAR-T细胞）治疗是治疗复发/难治性急性b淋巴细胞白血病的有效手段，CAR-T细胞治疗后的复发需要新的靶点解决。一项对194例急性b淋巴细胞白血病患者的回顾性分析显示CD123表达预后不良。为了提高疗效，在CAR-T细胞构建中，可以考虑CAR19与异常抗原（如CD123）结合，形成双特异性或多特异性抗原。背景：大约30% - 60%的急性b淋巴细胞白血病（B-ALL）患者表现为难治性或复发性，这是B-ALL患者死亡的主要原因之一，但治疗复发/难治性B-ALL （R/R B-ALL）的方法有限。嵌合抗原受体重定向T细胞（CAR-T细胞）对B-ALL具有很强的抗白血病作用。约90%接受CD19-CAR-T细胞治疗的R/R B-ALL患者获得完全缓解。然而，CAR-T细胞治疗后有60% ~ 70%的患者复发，这可能与靶抗原减少或逃逸有关。迫切需要新的产品来预防和治疗引起复发的抗原逃逸。患者与方法：本文回顾性分析本中心2010年1月至2015年12月首次诊断的B-ALL患者的免疫表型，确定抗原异常表达是否与患者预后相关，以期寻找新的免疫治疗靶点。结果：无异常抗原表达患者的无病生存期和总生存期均优于异常抗原表达患者。最常见的异常抗原是CD123、CD13和CD56。相关分析显示，CD123异常表达与无病生存期和总生存期均呈负相关。结论：因此，在R/R B-ALL患者CAR-T细胞构建中，常规CD19与CD123等异常抗原结合形成双特异性或多特异性CAR-T细胞可达到提高疗效的目的。然而，还需要更多的临床试验。
Chimeric antigen receptors redirected T cell (CAR-T cell) therapy is an effective means of treating relapsed/refractory acute B-lymphocytic leukemia, and new targets are needed to solve the recurrence after CAR-T cell treatment. A retrospective analysis of 194 patients with acute B-lymphocytic leukemia showed a poor prognosis for CD123 expression. To improve efficacy, CAR19 can be considered to bind to aberrant antigens such as CD123 to form a bispecific or multispecific antigen in CAR-T cell construction.Background: Approximately 30% to 60% of patients with acute B-lymphocytic leukemia (B-ALL) show as refractory or relapsed, which is one of the major causes of death in patients with B-ALL, but the methods of the treatment for relapsed/refractory B-ALL (R/R B-ALL) are limited. The chimeric antigen receptors redirected T cells (CAR-T cells) have showed a strong anti-leukemia role for B-ALL. About 90% of patients with R/R B-ALL treated with CD19-CAR-T cells achieved complete remission. However, 60% to 70% of patients relapsed after CAR-T cells treatment, which may be related to target antigen reduction or escape. New products are urgently needed to prevent and treat antigenic escapes causing recurrence. Patients and Methods: In this article, we retrospectively analyzed the immunophenotype of patients with B-ALL initially diagnosed in our center from January 2010 to December 2015 to determine whether aberrant antigen expression was associated with the prognosis of patients in order to find new targets for immunotherapy. Results: The results show that disease-free and overall survival in patients without aberrant antigen expression were better than patients with aberrant antigen expression. The most common abnormal antigens were CD123, CD13, and CD56. Correlation analysis showed a negative correlation between aberrant CD123 expression and both disease-free and overall survival. Conclusion: Therefore, in the construction of CAR-T cells in patients with R/R B-ALL, conventional CD19 can be combined with aberrant antigens such as CD123 to form CARs with bi-specific antigens or multi-specific antigens may achieve the purpose of improving efficacy. However, more clinical trials are needed.