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异体针对病毒特异性 T 细胞治疗实体器官移植后双链 DNA 病毒再激活和移植后淋巴增殖性疾病。

Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant.

机构信息

Division of Bone Marrow Transplant and Immune Deficiencies, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.

Division of Bone Marrow Transplant and Immune Deficiencies, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.

出版信息

Am J Transplant. 2024 Sep;24(9):1634-1643. doi: 10.1016/j.ajt.2024.04.009. Epub 2024 Apr 19.


DOI:10.1016/j.ajt.2024.04.009
PMID:38643944
Abstract

Reactivation or primary infection with double-stranded DNA viruses is common in recipients of solid organ transplants (SOTs) and is associated with significant morbidity and mortality. Treatment with conventional antiviral medications is limited by toxicities, resistance, and a lack of effective options for adenovirus (ADV) and BK polyomavirus (BKPyV). Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients, and no large studies have been published in the SOT population to date. In this study, we report on the outcome of quadrivalent third-party VST infusions in 98 recipients of SOTs in the context of an open-label phase 2 trial. The 98 patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for cytomegalovirus, 68% for ADV, and 61% for Epstein-Barr virus. Twenty percent of patients with posttransplant lymphoproliferative disorder had a complete response and 40% of patients had a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in SOT recipients.

摘要

双链 DNA 病毒在实体器官移植(SOT)受者中再激活或原发感染很常见,与重大发病率和死亡率相关。传统抗病毒药物的治疗受到毒性、耐药性以及腺病毒(ADV)和 BK 多瘤病毒(BKPyV)缺乏有效治疗选择的限制。病毒特异性 T 细胞(VST)已被证明是 ADV、BKPyV、巨细胞病毒(CMV)和 EBV 感染的有效治疗方法。这些研究大多在干细胞受者中进行,迄今为止,在 SOT 人群中尚未发表大型研究。在本研究中,我们报告了在一项开放标签 2 期试验背景下,98 例 SOT 受者接受四价第三方 VST 输注的结果。98 例患者共接受了 181 次输注,每位患者中位数接受 2 次输注。BKPyV 的总体缓解率为 45%,CMV 为 65%,ADV 为 68%,EBV 为 61%。移植后淋巴增殖性疾病患者中有 20%完全缓解,40%部分缓解。所有 VST 输注均耐受良好。我们的结论是,VST 在治疗 SOT 受者的病毒感染方面是安全有效的。

相似文献

[1]
Third-party virus-specific T cells for the treatment of double-stranded DNA viral reactivation and posttransplant lymphoproliferative disease after solid organ transplant.

Am J Transplant. 2024-9

[2]
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J Clin Oncol. 2017-11-1

[3]
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Transplant Cell Ther. 2023-5

[4]
Impact of antiviral prophylaxis on EBV viremia and posttransplant lymphoproliferative disorders in solid organ transplant recipients: a systematic review and meta-analysis.

Virol J. 2025-1-15

[5]
Epstein-Barr virus reactivation in allogeneic stem cell transplantation is highly related to cytomegalovirus reactivation.

Clin Transplant. 2013-6-19

[6]
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Blood. 2002-4-1

[7]
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Transpl Immunol. 2007-4

[8]
Infusions of Epstein-Barr virus-specific cytotoxic T lymphocytes as post-remission therapy in high-risk post-transplant lymphoproliferative disorder patients: report of two cases.

Int J Hematol. 2018-5

[9]
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Am J Transplant. 2014-2-19

[10]
Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant.

Blood Adv. 2022-9-13

引用本文的文献

[1]
T cell receptor-like antibody specifically targets and eliminates cells infected with cytomegalovirus.

J Transl Med. 2025-7-28

[2]
Lymphoproliferations in People Living with HIV: Oncogenic Pathways, Diagnostic Challenges, and New Therapeutic Opportunities.

Cancers (Basel). 2025-6-22

[3]
BK Virus-Specific T Cell Response Associated with HLA Genotypes, RhD Status, and CMV or EBV Serostatus in Healthy Donors for Optimized Cell Therapy.

J Clin Immunol. 2025-6-19

[4]
A Phase I Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against BK-Virus in Adult Kidney Transplant Recipients.

J Med Virol. 2025-4

[5]
The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation.

Transplantation. 2025-7-1

[6]
Donor Variability and PD-1 Expression Limit BK Polyomavirus-specific T-cell Function and Therapy.

Transplantation. 2025-9-1

[7]
Seraph 100 Microbind Affinity Blood Filter for Persistent Pediatric BK Virus Nephropathy.

Pediatr Transplant. 2025-5

[8]
Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation.

Microorganisms. 2024-12-30

[9]
Stem cell memory EBV-specific T cells control EBV tumor growth and persist in vivo.

Sci Adv. 2024-8-23

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