EBV-related lymphomas: new approaches to treatment.
EBV-related lymphomas: new approaches to treatment.
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DOI：
10.1007/s11864-013-0231-y
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发表时间：
2013-06
影响因子：
4.3
通讯作者：
Ambinder, Richard F.
中科院分区：
文献类型：
--
作者：
Kanakry, Jennifer A.;Ambinder, Richard F.
关键词：
在EB病毒（EBV）相关淋巴瘤的治疗中，很少有专门针对这些肿瘤内潜伏病毒的治疗方法;在大多数情况下，治疗方法与EBV阴性淋巴瘤的方法没有什么不同。尽管如此，目前和新兴的疗法集中在利用EBV生物学方面，可能会在未来为EBV阳性淋巴瘤提供更有针对性的策略。从概念上讲，EBV特异性方法包括用疫苗或EBV特异性细胞毒性T淋巴细胞支持抗病毒/抗肿瘤免疫应答，激活裂解病毒基因以使肿瘤细胞对抗病毒治疗敏感，以及抑制可能被潜伏EBV蛋白激活的下游促存活或抗凋亡途径。EBV特异性细胞毒性T细胞输注已被证明对EBV相关的移植后淋巴组织增生性疾病（EBV-PTLD）有效，并将这种过继性免疫疗法扩展到其他EBV相关的恶性肿瘤是一个活跃的研究领域。然而，与EBV-PTLD相比，其他EBV相关的淋巴瘤通常具有更多限制性，更少的免疫原性病毒抗原阵列，以通过过继免疫疗法进行治疗靶向。此外，霍奇金淋巴瘤的恶性EBV阳性肿瘤细胞分散在调节性T细胞、巨噬细胞和其他细胞的密集浸润中，这些细胞可能抑制过继免疫疗法的抗肿瘤功效。克服这些障碍的策略是正在进行的临床前和临床研究的领域。一些新出现的治疗EB病毒相关淋巴瘤的方法包括将诱导裂解病毒复制的药物与抗疱疹病毒药物偶联，或使用小分子抑制剂阻断由EB病毒组成性激活的信号通路。EBV疫苗似乎最有希望用于治疗或预防EBV相关的恶性肿瘤，而不是预防原发性EBV感染。在残留或低体积EBV相关恶性肿瘤患者中进行的EBV疫苗试验或在等待实体器官移植的EBV血清阴性患者中预防EBV-PTLD的试验正在进行中。
Opinion statementIn the treatment of Epstein-Barr virus (EBV)-related lymphomas, there are few therapies specifically targeted against the latent virus within these tumors; in most cases the treatment approach is not different than the approach to EBV-negative lymphomas. Nonetheless, current and emerging therapies focused on exploiting aspects of EBV biology may offer more targeted strategies for EBV-positive lymphomas in the future. Conceptually, EBV-specific approaches include bolstering the antiviral/antitumor immune response with vaccines or EBV-specific cytotoxic T-lymphocytes, activating lytic viral genes to render the tumor cells susceptible to antiviral therapies, and inhibiting the downstream prosurvival or antiapoptotic pathways that may be activated by latent EBV proteins. EBV-specific cytotoxic T-cell infusions have proven effective in EBV-related posttransplantation lymphoproliferative disorder (EBV-PTLD) and expanding such adoptive immunotherapies to other EBV-related malignancies is an area of active research. However, other EBV-related lymphomas typically have more restricted, less immunogenic arrays of viral antigens to therapeutically target with adoptive immunotherapy compared with EBV-PTLD. Furthermore, the malignant EBV-positive tumor cells of Hodgkin lymphoma are scattered amid a dense infiltrate of regulatory T-cells, macrophages, and other cells that may dampen the antitumor efficacy of adoptive immunotherapy. Strategies to overcome these obstacles are areas of ongoing preclinical and clinical investigations. Some emerging approaches to EBV-related lymphomas include the coupling of agents that induce lytic viral replication with antiherpesvirus agents, or the use of small molecule inhibitors that block signaling pathways that are constitutively activated by EBV. EBV vaccines seem most promising for the treatment or prevention of EBV-related malignancies, rather than the prevention of primary EBV infection. EBV vaccine trials in patients with residual or low-bulk EBV-related malignancies or for the prevention of EBV-PTLD in EBV-seronegative patients awaiting solid organ transplantation are ongoing.
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影响因子：
3.7
作者：
Hatton O;Lambert SL;Krams SM;Martinez OM
通讯作者：
Martinez OM
影响因子：
7.6
作者：
Dargart, Jamie L.;Fish, Kamonwan;Gordon, Leo I.;Longnecker, Richard;Cen, Osman
通讯作者：
Cen, Osman
影响因子：
20.3
作者：
De Angelis, Biagio;Dotti, Gianpietro;Savoldo, Barbara
通讯作者：
Savoldo, Barbara
DOI：
10.1124/jpet.106.109058
发表时间：
2006-12-01
影响因子：
3.5
作者：
Braselmann, Sylvia;Taylor, Vanessa;Masuda, Esteban S.
通讯作者：
Masuda, Esteban S.
影响因子：
11.5
作者：
Gandhi, MK;Lambley, E;Khanna, R
通讯作者：
Khanna, R