A phase II study evaluating the safety and efficacy of an adenovirus-DLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma
A phase II study evaluating the safety and efficacy of an adenovirus-DLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma
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DOI：
10.1093/annonc/mdr341
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发表时间：
2012-04-01
影响因子：
50.5
通讯作者：
Toh, H. C.
中科院分区：
文献类型：
--
作者：
Chia, W. K.;Wang, W. -W.;Toh, H. C.
背景：转移性EB病毒（EBV）阳性鼻咽癌（NPC）患者的预后仍然很差。为了评估树突状细胞（DC）疫苗靶向NPC细胞表达的亚显性EBV抗原LMP 1和LMP 2的能力，我们使用用编码截短的LMP 1（Delta LMP 1）和全长LMP 2（Ad-Delta LMP 1-LMP 2）的腺病毒转导的自体DC接种患者。每两周一次，最多五次。毒性，免疫反应和临床responsesdetermined.Results：大多数患者有广泛的疾病，中位数为三个内脏部位的参与（范围1-7）。未观察到显著毒性。Ad-Delta LMP 1-LMP 2 DC在1/2名患者中的9名中诱导迟发型超敏反应，但是尽管这些DC在体外激活LMP 1/2特异性T细胞，但未检测到外周LMP 1/2特异性T细胞频率的增加。结论：Ad-Delta LMP 1-LMP 2转导的DC可成功地用于晚期NPC患者的治疗。由于疗效有限，未来的研究应集中在DC疫苗具有更大的效力，给予受试者与肿瘤负荷较低。
Background: Individuals with metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. To evaluate the ability of a dendritic cell (DC) vaccine to target subdominant EBV antigens LMP1 and LMP2 expressed by NPC cells, we vaccinated patients using autologous DCs transduced with an adenovirus encoding a truncated LMP1 (Delta LMP1) and full-length LMP2 (Ad-Delta LMP1-LMP2).Materials and methods: Sixteen subjects with metastatic NPC received Ad-Delta LMP1-LMP2 DC vaccines i.d. biweekly for up to five doses. Toxicity, immune responses and clinical responses were determined.Results: Most patients had extensive disease, with a median of three visceral sites of involvement (range 1-7). No significant toxicity was observed. Ad-Delta LMP1-LMP2 DCs induced delayed type hypersensitivity responses in 9 out of 12 patients, but although these DCs activated LMP1/2-specific T cells in vitro, no such increase in the frequency of peripheral LMP1/2-specific T cells was detected. Three patients had clinical responses including one with partial response (for 71/2 months) and two with stable disease (for 61/2 and 71/2 months).Conclusions: Ad-Delta LMP1-LMP2 transduced DCs can be successfully generated and safely administered to patients with advanced NPC. Since efficacy was limited, future studies should focus on DC vaccines with greater potency administered to subjects with less tumor burden.