Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma
Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma
复制标题
DOI：
10.1038/s41467-020-17175-8
复制
发表时间：
2020-07-15
影响因子：
16.6
通讯作者：
Ahmed, Nabil
中科院分区：
文献类型：
--
作者：
Hegde, Meenakshi;Joseph, Sujith K.;Ahmed, Nabil
难治性转移性横纹肌肉瘤基本上是无法治愈的。在这里，我们分析了一例患有难治性骨髓转移性横纹肌肉瘤的儿童对自体HER2CAR T细胞的反应。在淋巴耗竭化疗后给予三个周期的HER2 CAR T细胞可诱导缓解，这种缓解通过再注射四次CAR T细胞而不会耗尽淋巴而得到巩固。纵向免疫监测显示T细胞受体谱系重塑，免疫优势克隆和血清自身抗体对致癌信号通路蛋白起反应。这种疾病在停止治疗六个月后在骨髓中复发。第二次缓解是在淋巴衰竭和HER2 CAR T细胞的一个周期后实现的。用额外的CAR T细胞输注巩固反应包括培溴利珠单抗，以提高他们的疗效。这里描述的患者是正在进行的I期试验(NCT00902044；活跃，非招募)的参与者，在本报告发表时，他已经接受T细胞输注20个月，没有发现任何疾病。复发的转移性横纹肌肉瘤在很大程度上仍无法治愈。在这里，作者描述了一个患有转移性横纹肌肉瘤的儿童，他对HER2特异性CAR T细胞有持久的反应，并显示出内源性免疫反应。
Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report. Recurrent metastatic rhabdomyosarcoma remains largely incurable. Here, the authors describe a child with metastatic rhabdomyosarcoma who has durable response to HER2-specific CAR T cells and shows endogenous immune reactivity.