Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy
Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy
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DOI：
10.1182/blood.v99.11.3916
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发表时间：
2002-06-01
期刊：
影响因子：
20.3
通讯作者：
Hebart, H
中科院分区：
文献类型：
--
作者：
Einsele, H;Roosnek, E;Hebart, H
我们过继性地将供体来源的巨细胞病毒（CMV）特异性t细胞系转移到8名缺乏CMV特异性t细胞增殖的干细胞移植受者体内。所有患者（其中1例感染了基因典型地对更昔洛韦耐药的巨细胞病毒毒株）均接受了4周以上未成功的抗病毒化疗。CMV特异性细胞系是通过CMV抗原的重复刺激制备的，它增加了CMV特异性T细胞的百分比，即使对1到3种HLA抗原不匹配的患者也完全降低了同种异体反应性。移植后平均120天（范围79-479天）移植10(7)个T细胞/m(2)，未发现任何副作用。尽管停止了抗病毒化疗，所有7例可评估患者的巨细胞病毒载量均显著下降，最大降幅中位数为20天（范围5-31天）。在2例病毒载量高的患者中，抗病毒效果只是短暂的。其中一名患者接受了第二次t细胞输注，彻底清除了病毒。在移植后的中位11天，6例患者出现cmv特异性T细胞增殖，5例患者出现cmv特异性CD4(+) T细胞增加。在6例患者中，在移植后的中位数13天检测到1.12至41个cmv特异性CD8(+) T细胞/muL，在移植前缺乏cmv特异性CD8+ T细胞的所有患者中检测到的cmv特异性CD8+ T细胞均增加。因此，抗巨细胞病毒细胞治疗在7例患者中有5例成功，而在t细胞治疗期间或之后接受强化免疫抑制的7例患者中有2例仅获得短暂的病毒载量降低。(C) 2002年由美国血液病学会出版。
We adoptively transferred donor-derived cytomegalovirus (CMV)-specific T-cell lines into 8 stem cell transplant recipients lacking CMV-specific T-cell proliferation. All patients, of whom one was infected by a CMV strain that was genotypically ganciclovir resistant, had received unsuccessful antiviral chemotherapy for more than 4 weeks. CMV-specific lines had been prepared by repetitive stimulation with CMV antigen, which increased the percentage of CMV-specific T cells and ablated alloreactivity completely even against patients mismatched for 1 to 3 HLA antigens. After transfer of 10(7) T cells/m(2) at a median of 120 days (range, 79-479 days) after transplantation, no side effects were noticed. Despite cessation of antiviral chemotherapy, the CMV load dropped significantly in all 7 evaluable patients, with a maximal reduction after a median of 20 days (range, 5-31 days). In 2 patients with high virus load, the antiviral effect was only transient. One of these patients received a second T-cell infusion, which cleared the virus completely. At a median of 11 days after transfer, CMV-specific T-cell proliferation was demonstrated in 6 patients, and an increase in CMV-specific CD4(+) T cells was demonstrated in 5 patients. In 6 patients, 1.12 to 41 CMV-specific CD8(+) T cells/muL blood were detected at a median of 13 days after transfer, with an increase in all patients lacking CMV-specific CD8+ T cells prior to transfer. Hence, anti-CMV cellular therapy was successful in 5 of 7 patients, whereas In 2 of 7 patients, who received an intensified immune suppression at the time of or after T-cell therapy, only transient reductions In virus load were obtained. (C) 2002 by The American Society of Hematology.