Immunity, homing and efficacy of allogeneic adoptive immunotherapy for posttransplant lymphoproliferative disorders
Immunity, homing and efficacy of allogeneic adoptive immunotherapy for posttransplant lymphoproliferative disorders
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DOI：
10.1111/j.1600-6143.2007.01796.x
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发表时间：
2007-05-01
影响因子：
8.8
通讯作者：
Crawford, D. H.
中科院分区：
文献类型：
--
作者：
Gandhi, M. K.;Wilkie, G. M.;Crawford, D. H.
自体EB病毒(EBV)特异性细胞毒性T淋巴细胞(Auto-CTL)过继免疫治疗可缓解移植后淋巴增生性疾病(PTLD)。AUTO-CTL的广泛适用性仍然受到限制。生成是耗时的，在接受B细胞耗竭抗体利妥昔单抗治疗的患者中不能建立自动CTL。相比之下，预先生成的同种异体CTL(allo-CTL)提供了即时的可及性。此前，Allo-CTL已在“早期”多克隆PTLD中显示出疗效。我们治疗了3例实体器官移植后发生侵袭性的晚期单克隆性PTLD患者。所有这些都对至少三种先前的治疗方法无效。尽管人类白细胞抗原存在差异，但毒性可以忽略不计，早期体内抗病毒效果和EBV多肽特异性免疫重建。2例患者完全缓解(CR)。一例在治疗17个月后仍留在CR中，与供者来源的肿瘤靶向EBV特异性CTL的持续存在一致；另一例死于非PTLD相关的病理。在第三例患者中，尸检显示异基因CTL在肿瘤部位归巢。对PTLD中EBV特异性的allo-CTL进行更大规模的前瞻性研究是必要的。
Adoptive immunotherapy using autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (auto-CTL) can regress posttransplant lymphoproliferative disorders (PTLD). Widespread applicability of auto-CTL remains constrained. Generation is time-consuming, and auto-CTL cannot be established in patients treated with the B-cell depleting antibody rituximab. By contrast, pregenerated allogeneic CTL (allo-CTL) offers immediate accessibility. Allo-CTL has previously shown efficacy in "early" polyclonal- PTLD. We treated three patients with aggressive, advanced monoclonal-PTLD following solid-organ transplantation. All were refractory to at least three prior therapies. Despite HLA disparity, there was negligible toxicity, with early in vivo antiviral efficacy and reconstitution of EBV peptide-specific immunity. Two patients attained complete remission (CR). One remains in CR 17 months following therapy, coincident with persistence of donor-derived tumor targeted EBV-specific CTL; the other died of non-PTLD related pathology. In the third patient, autopsy demonstrated homing of allo-CTL at the tumor site. Larger prospective studies of EBV-specific allo-CTL in PTLD are warranted.