Adoptive immunotherapy for EBV-associated malignancies
Adoptive immunotherapy for EBV-associated malignancies
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DOI：
10.1080/10428190400002202
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发表时间：
2005-01-01
影响因子：
2.6
通讯作者：
Rooney, CM
中科院分区：
文献类型：
--
作者：
Gottschalk, S;Heslop, HE;Rooney, CM
潜伏性EB病毒(EBV)感染与多种恶性肿瘤有关，包括Burkitt淋巴瘤、霍奇金病、鼻咽癌和淋巴增生性疾病。在这些肿瘤中表达的EBV蛋白为抗原特异性细胞毒性T细胞(CTL)的过继免疫治疗提供了靶点，EBV特异性CTL已成功地用于预防和治疗造血干细胞移植(HSCT)后的EBV-LPD。EBV特异性CTL治疗其他EBV相关恶性肿瘤，如霍奇金氏病和鼻咽癌的临床经验有限，到目前为止获得的结果表明，EBV特异性CTL对HSCT后EBV-LPD的疗效不如EBV-LPD。CTL效率的降低很可能反映了肿瘤细胞的免疫逃避策略，如下调免疫优势的EBV蛋白和分泌抑制性细胞因子。为了克服这些免疫逃避策略，已经开发了许多方法，包括针对优势EBV抗原的CTL和通过基因修饰CTL来提高其效力。
Latent Epstein-Barr virus (EBV) infection is associated with a diverse group of malignancies including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), and lymphoproliferative disease (LPD). EBV proteins expressed in these malignancies provide targets for the adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL) and EBV-specific CTL have been used successfully for the prophylaxis and treatment of EBV-LPD post hematopoietic stem cell transplantation (HSCT). The clinical experience with EBV-specific CTL for other EBV-associated malignancies such as Hodgkin's disease and NPC is limited and the results obtained so far indicate that EBV-specific CTL are less effective than for EBV-LPD post HSCT. Decreased CTL efficacy most likely reflect immune evasion strategies by tumor cells such as down regulation of immunodominant EBV proteins and secretion of inhibitory cytokines. To overcome these immune evasion strategies a number of approaches have been developed including targeting CTL to subdominant EBV antigens and genetically modifying CTL to increase their potency.