Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation
Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation
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DOI：
10.1182/blood-2009-07-232454
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发表时间：
2009-11-05
期刊：
影响因子：
20.3
通讯作者：
Bollard, Catherine M.
中科院分区：
文献类型：
--
作者：
Leen, Ann M.;Christin, Anne;Bollard, Catherine M.
病毒感染或重新激活仍然是异基因干细胞移植后发病率和死亡率的主要原因。我们现在发现，对于接受部分人类白细胞抗原相合和半倍相合干细胞移植的儿童移植受者(n=13)，可以安全地输注对两种常见检测到的病毒-EB病毒(EBV)和腺病毒具有特异性的单个细胞毒性T淋巴细胞(CTL)株(5×10(6)-1.35×10(8)cell/m(2))，而不会诱发移植物抗宿主病。CTL的EBV特异性成分在体内扩张并持续超过12周，但腺病毒特异性成分只有在伴随腺病毒感染的情况下才在体内扩张。然而，即使在没有病毒感染的CTL受者中，在外周血液中也可以检测到至少8周的腺病毒特异性T细胞，前提是他们循环中的淋巴细胞中腺病毒特异性成分首先通过体外暴露于腺病毒抗原而扩增。在输注后，这13名高危受者中没有一人发生EBV相关淋巴增殖性疾病，而其中2名受试者的腺病毒疾病得到了缓解。因此，在人类白细胞抗原不匹配的干细胞移植后，同时含有EBV和腺病毒特异性T细胞的双特异性CTL可以安全地重建抗原响应性的CTL群体，并可能提供抗病毒活性。这项试验在www.Clinicaltrials.gov上注册为#NCT00590083。(血。2009；114：4283-4292)
Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 x 10(6)-1.35 x 10(8) cells/m(2)) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen-matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lympho-proliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive "memory" population of CTLs after human leukocyte antigen-mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at www.clinicaltrials.gov as #NCT00590083. (Blood. 2009; 114: 4283-4292)