Lin Chen-Lung, Lo Wei-Feng, Lee Tzong-Hsien, Ren Yi, Hwang Shiuh-Lin, Cheng Yu-Fan, Chen Chao-Long, Chang Yu-Sen, Lee Steve P, Rickinson Alan B, Tam Paul Kwong Hang
Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, 883 Taiwan.
Cancer Res. 2002 Dec 1;62(23):6952-8.
Nasopharyngeal carcinoma (NPC), a common neoplasm in Southeast Asia, is EBV-positive and expresses a limited number of antigens, including latent membrane protein 2. In this study, autologous monocyte-derived dendritic cells were cultured from patients with advanced NPC, matured with cytokine, pulsed with HLA-A1101-, A2402-, or B40011-restricted epitope peptides from EBV latent membrane protein 2 and injected into inguinal lymph nodes. Sixteen patients with local recurrence or distant metastasis after conventional therapies received four injections at weekly intervals. Epitope-specific CD8+ T-cell responses were elicited or boosted in 9 patients receiving HLA-A1101- or A2402-restricted peptides, with stronger responses seen to the A1101 peptide. Furthermore, epitope-specific cytotoxicity was detectable in peripheral blood T cells harvested at 3-months after vaccination from A1101-responsive patients, and in 2 patients, this coincided with partial tumor reduction. Approaches leading to stronger and more sustained EBV-specific T-cell responses, therefore, may have therapeutic potential in the context of NPC.
鼻咽癌(NPC)是东南亚地区的一种常见肿瘤,呈EB病毒阳性,表达包括潜伏膜蛋白2在内的少数抗原。在本研究中,从晚期鼻咽癌患者中培养出自体单核细胞衍生的树突状细胞,用细胞因子使其成熟,用来自EB病毒潜伏膜蛋白2的HLA - A1101、A2402或B40011限制性表位肽进行脉冲处理,然后注入腹股沟淋巴结。16例经传统治疗后出现局部复发或远处转移的患者每隔一周接受4次注射。在接受HLA - A1101或A2402限制性肽的9例患者中引发或增强了表位特异性CD8 + T细胞反应,对A1101肽的反应更强。此外,在接种疫苗3个月后采集的A1101反应性患者的外周血T细胞中可检测到表位特异性细胞毒性,在2例患者中,这与肿瘤部分缩小相吻合。因此,导致更强和更持久EB病毒特异性T细胞反应的方法在鼻咽癌的治疗中可能具有潜力。