Glycoprotein 350-targeted chimeric antigen receptor T-cell therapy for nonneoplastic chronic active EpsteinBarr virus infection:a case report,2024,Liu

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Case Report
Glycoprotein 350-targeted chimeric antigen receptor T-cell therapy for nonneoplastic chronic active Epstein-Barr virus infection: a case report
Yandi Liu1#, Jiaoyang Cai2#, Tianyi Wang2, Jing Wang1, Yanjing Tang2, Xinyu Wan2, Wenjie Li2, Benshang Li2, Qing Cao1

1Department of Infectious Diseases, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Hematology/Oncology, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Contributions: (I) Conception and design: Q Cao, B Li; (II) Administrative support: Q Cao, B Li; (III) Provision of study materials or patients: T Wang; (IV) Collection and assembly of data: Y Liu; (V) Data analysis and interpretation: Y Liu, J Cai; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work as co-first authors.

Correspondence to: Qing Cao, MD, PhD. Department of Infectious Diseases, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China. Email: caoqing@scmc.com.cn; Dr. Benshang Li, MD, PhD. Department of Hematology/Oncology, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China. Email: libenshang@scmc.com.cn.
Background: 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 5.99×106 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.

Conclusions: 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.

Keywords: Chimeric antigen receptor T-cells therapy (CAR T-cells therapy); Epstein-Barr virus infection (EBV infection); chronic active Epstein-Barr virus infection (CAEBV infection); case report

Submitted Jul 30, 2024. Accepted for publication Dec 03, 2024. Published online Dec 27, 2024.