Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy.
Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy.
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DOI：
10.3389/fimmu.2020.581116
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发表时间：
2020
影响因子：
7.3
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Wang K;Zhao Y;Wang X;Wang B;Qin M;Zhu G;Wu H;Liu Z;Zheng X;Zheng H;Chen Z
CD 19嵌合抗原受体T细胞（CD 19 CAR-T）在治疗急性B细胞淋巴母细胞白血病（B-ALL）和B细胞淋巴瘤方面显示出巨大的潜力，抗CD 19单链抗体大多来源于鼠源抗体序列。然而，约10-20%的B-ALL患者表现出对基于鼠的CD 19 CAR-T（CD 19 mCAR-T）的原发性耐药。在此，我们报告了人源化选择性CD 19 CAR-T（CD 19 hsCAR-T）可能为这个问题提供解决方案。一名10岁的男孩在3月被诊断出患有高危B-ALL，2013年10月复发，2018年，他在2017年接受了单倍相合造血干细胞移植（HSCT）。然后，患者在使用阿贝斯汀、地塞米松和天冬酰胺酶（VDL）诱导化疗后接受了两次单倍体相同的CD 19 mCAR-T输注，但未观察到应答。我们在用长春地辛、艾达鲁肽、地塞米松和聚乙二醇化天冬酰胺酶（VDLD）加硼替佐米化疗后进一步用CD 19 hsCAR-T治疗该患者。该患者达到了最小残留疾病阴性（MRDneg）完全缓解伴造血功能不完全恢复（CRi），并保持CRi超过8个月，副作用可控。不幸的是，患者于2020年1月25日死于不明肺部感染。CD 19 hsCAR-T可能有潜力诱导主要对CD 19 mCAR-T难治的患者缓解。
CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10–20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem. A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020. CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.
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影响因子：
11.5
作者：
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通讯作者：
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影响因子：
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28.5
作者：
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Grupp SA
DOI：
10.1038/s41571-019-0184-6
发表时间：
2019-06
期刊：
Nature reviews. Clinical oncology
影响因子：
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作者：
Shah NN;Fry TJ
通讯作者：
Fry TJ
影响因子：
12.8
作者：
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