Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes
Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes
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DOI：
10.1200/jco.2005.02.6195
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发表时间：
2005-12-10
影响因子：
45.3
通讯作者：
Siena, S
中科院分区：
文献类型：
--
作者：
Comoli, P;Pedrazzoli, P;Siena, S
目的鼻咽癌（NPC）是一种表达EBV抗原的与eb病毒（EBV）相关的恶性肿瘤，这些EBV抗原可能是细胞治疗的靶点，包括潜伏膜蛋白2 （LMP2）。我们进行了ebv靶向细胞治疗的临床试验，使用自体病毒特异性细胞毒性T淋巴细胞（ctl）治疗传统治疗难治性鼻咽癌。患者与方法10例常规放化疗后进展的ebv相关IV期鼻咽癌患者，通过ebv转化的自体b淋巴母细胞样细胞系（LCL）刺激，从外周血淋巴细胞中静脉注射ebv特异性ctl，再激活并体外扩增。结果所有患者均可产生EBV特异性ctl，主要是CD3(+)/CD8(+) T淋巴细胞，可特异性杀伤自体EBV- lcl、自体鼻咽癌细胞以及携带EBV抗原LMP2的自体靶标。患者接受2至23次ebv特异性ctl输注，除了2例肿瘤部位出现1至2级炎症反应外，这些ctl耐受性良好。10例患者中有6例疾病进展得到控制（2例部分缓解，4例病情稳定）。干扰素- γ产生细胞的分析显示ebv特异性免疫频率增加，4例患者出现lmp2特异性应答，其中3例具有临床益处。结论ebv靶向的自体ctl细胞治疗是安全的，可诱导lmp -2特异性免疫反应，并与常规治疗耐药的IV期鼻咽癌患者的客观反应和疾病进展控制相关。
Purpose Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related malignancy expressing EBV antigens that are possible targets of cell therapy, including latent membrane protein 2 (LMP2). We conducted a clinical trial of EBV-targeted cell therapy with autologous virus-specific cytotoxic T lymphocytes (CTLs) for NPC refractory to conventional treatments.Patients and Methods Ten patients with EBV-related stage IV NPC in progression after conventional radiotherapy and chemotherapy received intravenously autologous EBV-specific CTLs reactivated and expanded ex vivo from peripheral blood lymphocytes through stimulation with EBV-transformed autologous B-lymphoblastoid cell lines (LCL). Toxicity, specific cellular immune responses, and clinical tumor responses were evaluated,Results EBV-specific CTLs could be generated in all patients and were predominantly CD3(+)/CD8(+) T lymphocytes displaying specific killing of autologous EBV-LCL, autologous NPC cells as well as autologous targets bearing the EBV antigen LMP2. Patients received two to 23 infusions of EBV-specific CTLs that were well tolerated with the exception of grade 1 to 2 inflammatory reactions at the tumor site in two cases. Control of disease progression was obtained in six of 10 patients (two with partial response and four with stable disease). Analysis of interferon-gamma-producing cells demonstrated an increased frequency of EBV-specific immunity, with appearance of LMP2-specific responses in four patients, of whom three had clinical benefit.Conclusion Cell therapy with EBV-targeted autologous CTLs is safe, induces LMP-2-specific immunologic responses, and is associated with objective responses and control of disease progression in patients with stage IV NPC resistant to conventional treatments.