EB病毒相关肿瘤的免疫治疗

Immunotherapy for EBV- Related Neoplasms

EB病毒与人类多种肿瘤密切相关,包括移植后淋巴细胞增生症(PTLD)、伯基特淋巴瘤(BL)、艾滋病(AIDS)、部分鼻咽癌(NPC)及霍奇金病(HD)。由于传统放化疗不良反应明显且对顽固性或复发性肿瘤疗效甚微,故肿瘤免疫治疗显得十分重要。肿瘤细胞中EBV感染特性决定了抗原表达类型及细胞免疫靶向。免疫治疗策略从剔除EBV感染B细胞,如抗-B细胞单克隆抗体,延伸至恢复正常细胞免疫,包括过继性细胞毒性T淋巴细胞(CTL)治疗、肿瘤疫苗及基因治疗。尽管过继性CTLs治疗PTLD的先期成功,引导当今研究评估其治疗NPC和HD的可行性及有效性,但因转移T细胞短暂的持续性及肿瘤逃避机制而限制了T细胞疗法的广泛开展。此外,基于体外培养基础上的T细胞治疗,在肿瘤高发的发展中地区无法广泛应用,故肿瘤疫苗和基因治疗需进一步提高。总之,当前仍需要可从遗传学上改善输注T细胞功能及调整宿主内环境的有效策略。同理于肿瘤疫苗和基因治疗,需要一个更谨慎,适合批量生产及最终可进行人体注射的方法来发展针对EBV相关肿瘤的疫苗和基因治疗。本文综述了目前国内外针对EBV相关肿瘤免疫治疗的机制及现状。

Epstein-Barr virus （EBV） is closely related to several human malignancies, including post-transplant lymphoproliferative disease （PTLD）, Burkitt＇s lymphoma （BL）, and acquired immune deficiency syndrome （AIDS）. It is also associated with a subset of patients with nasopharyngeal carcinoma （NPC） and Hodgkin＇s disease （HD）. Owing to obvious side effects from radiation therapy and chemotherapy and minimal therapeutic efficacy for refractory or recurrent tumors, tumor immunotherapy becomes especially important. The nature of EBV infection in the malignant cell determines the pattern of antigen expression and the associated presence of targets for cellular immunotherapy. Immunotherapeutic strategies include elimination of the infected-B cells using anti-B cell monoclonal antibodies and restoration of normal cellular immunity that would be achieved by adoptive transplant cytotoxic T lymphocytes （CTLs） therapy, tumor vaccines and gene therapy. Although initial success with adoptive transplant CTLs for PTLD has led to current studies examining its feasibility and efficacy in NPC and HD, T cell therapies are limited by inadequate persistence of transferred T cells and by tumor evasion of the immune response. Additionally, T-cell therapies based on cell culture in vitro fail to be widely used in developing countries. Therefore further development of the tumor vaccines and gene therapy is needed. Development of strategies to genetically improve the function of infused T cells and modulate the host environment is still needed. EBV-related tumor vaccines and gene therapy require an even more cautious approach in their development. This paper reviews the mechanisms and current usage of immunotherapy for EBV-related neoplasms in China and overseas.