Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.
Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers.
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通过HLA肽四聚体选择后，巨细胞病毒特异性CTL转移给干细胞移植患者。
DOI：
10.1084/jem.20040613
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发表时间：
2005-08-01
影响因子：
15.3
通讯作者：
Moss, PAH
中科院分区：
文献类型：
--
作者：
Cobbold, M;Khan, N;Pourgheysari, B;Tauro, S;McDonald, D;Osman, H;Assenmacher, M;Billingham, L;Steward, C;Crawley, C;Olavarria, E;Goldman, J;Chakraverty, R;Mahendra, P;Craddock, C;Moss, PAH
干细胞移植广泛应用于一系列造血系统疾病的治疗。在移植后早期，患者的免疫功能受到严重抑制，巨细胞病毒（CMV）的再激活仍然是发病率和死亡率的重要原因。供体来源的cmv特异性CD8+ T细胞克隆的过继转移已被证明可降低病毒再激活率；然而，这种方法的复杂性严重限制了其临床应用。我们从干细胞移植供者的血液中纯化了cmv特异性CD8+ T细胞，使用hla -肽四聚体染色，然后用磁珠选择。在选择后的4小时内，将cmv特异性CD8+细胞直接输注到9例患者体内。中位细胞剂量为8.6 × 103/kg，纯度为98%。所有患者在输注后10天内均可检测到cmv特异性CD8+ T细胞，TCR克隆型分析显示两名患者输注细胞持续存在。每个病例的巨细胞病毒血症都减少了，8名患者清除了感染，其中包括一名有长期巨细胞病毒感染史的患者，对抗病毒治疗无效。这种新的过继转移方法在抗原特异性T细胞治疗中具有相当大的潜力。
Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA–peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 × 103/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.
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影响因子：
82.9
作者：
Heslop, HE;Ng, CYC;Rooney, CM
通讯作者：
Rooney, CM
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM
影响因子：
20.3
作者：
Einsele, H;Roosnek, E;Hebart, H
通讯作者：
Hebart, H
影响因子：
82.9
作者：
Kern, F;Surel, IP;Volk, HD
通讯作者：
Volk, HD
影响因子：
20.3
作者：
Chakraverty, R;Peggs, K;Mackinnon, S
通讯作者：
Mackinnon, S