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靶向糖蛋白 350 的 CAR-T 细胞治疗非肿瘤性慢性活动性 EB 病毒感染:一例病例报告

英文原题:Glycoprotein 350-targeted chimeric antigen receptor T-cell therapy for nonneoplastic chronic active Epstein-Barr virus infection: a case report.

查看英文原题

Glycoprotein 350-targeted chimeric antigen receptor T-cell therapy for nonneoplastic chronic active Epstein-Barr virus infection: a case report.

PubMed 2024/12/27(内容时间) Transl Pediatr Q2 · IF 2(JCR 2025)

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研究概要

我们的病例报告显示,CAR-T 细胞疗法治疗儿童 CAEBV 相对安全有效,与恶性肿瘤相比,CRS 更轻微。然而,需要更多病例来进一步评估疗效和安全性。

研究思路结论见上方概要

慢性活动性EB病毒(CAEBV)感染是一种罕见疾病,EB病毒(EBV)持续存在并复制,导致慢性症状和致命并发症。CAEBV的治疗仍在不断发展。我们的病例报告展示了一种治疗CAEBV的新疗法。病例描述:一名14岁男孩,有10个月反复腹泻、间歇性发热、腹痛、腹胀、头晕和乏力病史。体格检查发现包括严重营养不良和肝脾肿大。当地医院的检查结果显示,外周血EBV DNA载量为5.99 10 6 copies/mL。尽管接受了阿昔洛韦、化疗和支持治疗,症状仍持续存在。我们通过荧光定量聚合酶链反应测定了EBV感染的淋巴细胞亚型,以及外周血淋巴细胞中EBV包膜糖蛋白350(gp350)的表达。EBV不仅感染B细胞,还感染T细胞和NK细胞。根据临床表现、EBV DNA水平升高和EBV编码小RNA(EBER)阳性状态,患者被诊断为CAEBV感染。患者接受了氟达拉滨和环磷酰胺的预处理方案,以及gp350靶向CAR-T(CAR-T)细胞的静脉输注。输注后,患者出现I级细胞因子释放综合征(CRS),并于10天后出院。随访期间,EBV-DNA计数保持不可检测。

展开英文摘要原文

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease in which the Epstein-Barr virus (EBV) persists and replicates, causing chronic symptoms and fatal complications. The treatment of CAEBV is still evolving. Our case report showed a new therapy for CAEBV. CASE DESCRIPTION: A 14-year-old boy presented with a 10-month history of recurrent diarrhea, intermittent fever, abdominal pain, distension, dizziness, and fatigue. Physical examination findings included severe malnutrition and hepatosplenomegaly. The local hospital's test results showed that the load of EBV DNA in peripheral blood was 5.99 10 6 copies/mL. Despite treatment with acyclovir, chemotherapy, and supportive care, the symptoms persisted. We determined the lymphocyte subtypes of EBV infection by fluorescence quantitative polymerase chain reaction and the expression of EBV envelope glycoprotein 350 (gp350) in peripheral blood lymphocytes. EBV not only infects B cells but also T and NK cells. According to the clinical manifestations, elevated EBV DNA levels, and positive EBV-encoded small RNA (EBER) status, the patient was diagnosed with CAEBV infection. The patient received a conditioning regimen of fludarabine and cyclophosphamide and an intravenous infusion of gp350-targeted chimeric antigen receptor T (CAR T) cells. After infusion, the patient developed grade I cytokine release syndrome (CRS) and was discharged 10 days later. During the follow-up, the EBV-DNA count remained undetectable.

Our case report showed that CAR T-cell therapy is relatively safe and effective for treating CAEBV in children, with milder CRS compared to that in malignant tumors. However, a greater number of cases are needed to further evaluate the efficacy and safety.

论文信息

作者
Liu Y、Cai J、Wang T、Wang J、Tang Y、Wan X、Li W、Li B
单位
Department of Infectious Diseases, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.China
文献类型
病例报告
期刊
Translational pediatrics2024 Dec 31
原文标识
PubMed 39822998 · DOI 10.21037/tp-24-292