Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target.
Epstein Barr virus-associated lymphoproliferative diseases: the virus as a therapeutic target.
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DOI：
10.1038/emm.2014.102
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发表时间：
2015-01-23
影响因子：
12.8
通讯作者：
Kwong, Yok-Lam
中科院分区：
文献类型：
--
作者：
Tse, Eric;Kwong, Yok-Lam
eb病毒（EBV）相关淋巴增生性疾病（lpd）在免疫缺陷患者中表达所有EBV潜伏抗原（III型潜伏期），在免疫正常患者中表达有限抗原（I型和II型潜伏期）。移植后淋巴细胞增生性疾病（PTLD）是III型EBV潜伏期的原型。尽管EBV抗原具有高度的免疫原性，但由于潜在的免疫抑制，PTLD细胞增殖仍然不受控制。通过自体或异体来源的ebv特异性T细胞恢复抗ebv免疫已被证明是安全有效的。细胞治疗可以通过建立人类白细胞抗原特征的异基因ebv特异性T细胞库来改善。在表现为I型和II型潜伏期的EBV+ lpd中，EBV特异性T细胞的使用更为有限，尽管这种疗法的安全性和有效性也已得到证实。随着单克隆抗体和其他靶向治疗的出现，EBV特异性T细胞在EBV+ lpd中的治疗作用需要重新进行批判性评估。另一种策略涉及使用表观遗传学方法，当病毒胸苷激酶的表达使宿主肿瘤细胞对更昔洛韦的细胞毒性作用敏感时，诱导EBV进行裂解性增殖。最后，预防性使用抗病毒药物防止EBV再激活可能会减少EBV+ lpd的发生。
Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.
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