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Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel
Pediatric Hematology and Oncology ( IF 1.2 ) Pub Date : 2022-02-09 , DOI: 10.1080/08880018.2022.2035864
Oren M Gordon 1 , Madeline Terpilowski 2 , Robin Dulman 3 , Michael D Keller 1, 2 , Peter D Burbelo 4 , Jeffrey I Cohen 5 , Catherine M Bollard 1, 2 , Hema Dave 1, 2
Affiliation  

Abstract

Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting. We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia. Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.



中文翻译:

接受 tisagenlecleucel 治疗的 B 细胞 ALL 儿科患者对 SARS-CoV-2 的强烈免疫反应

摘要

由于长期 B 细胞发育不全和免疫抑制,嵌合抗原受体 (CAR)-T 细胞等抗 CD19 靶向治疗的接受者被认为面临复杂的严重急性呼吸综合征冠状病毒 (SARS-CoV-2) 感染的高风险。这些患者代表了一个独特的群体,到目前为止,在这种情况下,对 SARS-CoV-2 的免疫反应尚未得到很好的表征。我们报告了一名患有 B 细胞急性淋巴细胞白血病 (B-ALL) 的儿科患者,他在接受 blinatumomab 时出现了无症状的 SARS-CoV-2 感染,随后接受了淋巴清除 (LD) 和 tisagenlecleucel,这是一种针对 CAR-T 疗法的 CD19。该患者对 tisagenlecleucel 有完全反应,在治疗期间没有出现细胞因子释放综合征或 SARS-CoV-2 恶化。尽管 B 细胞发育不全,患者有证据表明 LD 后 IgG 抗体对尖峰和核衣壳的反应持续存在,随后是 tisagenlecleucel。此外,我们能够在 CAR-T 后的几个月内检测到识别多种病毒结构蛋白的 SARS-CoV-2 特异性 T 细胞。T 细胞反应是多功能的,主要是 CD4 限制的。该数据对于了解免疫系统受损患者的 SARS-CoV-2 免疫力以及 SARS-CoV-2 特异性 T 细胞疗法在治疗接受 B 细胞耗竭疗法的血癌患者中的潜在应用具有重要意义。此外,我们能够在 CAR-T 后的几个月内检测到识别多种病毒结构蛋白的 SARS-CoV-2 特异性 T 细胞。T 细胞反应是多功能的,主要是 CD4 限制的。该数据对于了解免疫系统受损患者的 SARS-CoV-2 免疫力以及 SARS-CoV-2 特异性 T 细胞疗法在治疗接受 B 细胞耗竭疗法的血癌患者中的潜在应用具有重要意义。此外,我们能够在 CAR-T 后的几个月内检测到识别多种病毒结构蛋白的 SARS-CoV-2 特异性 T 细胞。T 细胞反应是多功能的,主要是 CD4 限制的。该数据对于了解免疫系统受损患者的 SARS-CoV-2 免疫力以及 SARS-CoV-2 特异性 T 细胞疗法在治疗接受 B 细胞耗竭疗法的血癌患者中的潜在应用具有重要意义。

更新日期:2022-02-09
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