一项针对不可切除原发性肝癌患者的基于自体树突状细胞免疫疗法的I期研究。
A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer.
作者信息
Iwashita Yukio, Tahara Kouichirou, Goto Shigeru, Sasaki Atsushi, Kai Seiichiro, Seike Masataka, Chen Chao-Long, Kawano Katsunori, Kitano Seigo
机构信息
Department of Surgery I, Oita Medical University, Hasama-machi, Japan.
出版信息
Cancer Immunol Immunother. 2003 Mar;52(3):155-61. doi: 10.1007/s00262-002-0360-9. Epub 2003 Feb 6.
BACKGROUND/AIMS: To evaluate the safety and feasibility of immunotherapy based on autologous dendritic cells (DC) for patients with unresectable primary liver cancer (PLC).
METHODS
A total of ten patients were enrolled and immunized with DCs. Autologous DCs were generated ex vivo in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Cells were then pulsed with tumor lysate (TL), tumor necrosis factor-alpha (TNF-alpha) and keyhole limpet hemocyanin (KLH). Non-adherent cells were collected on day 9 and cells were administered into the inguinal lymph node. Each patient received 1-10 x 10(6) cells four times at weekly intervals.
RESULTS
Immunization was well tolerated in all patients without significant toxicity. DC vaccination induced delayed-type hypersensitivity (DTH) against KLH in seven out of ten patients. In one patient, one of the two liver tumors (tumor in segment 7, 13 mm in diameter) decreased in size to 7 mm and showed necrotic change on computed tomography examination after eight immunizations. In two patients, serum levels of tumor markers decreased after vaccination.
CONCLUSION
The present clinical trial suggested that immunization by TL-pulsed DCs is feasible in patients with unresectable PLC without any toxicity. Further improvement in the clinical results of immunotherapy might be expected by modifying the therapeutic protocol.
背景/目的：评估基于自体树突状细胞（DC）的免疫疗法对不可切除原发性肝癌（PLC）患者的安全性和可行性。
方法
共纳入10例患者并使用DC进行免疫治疗。在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）存在的情况下，在体外生成自体DC。然后用肿瘤裂解物（TL）、肿瘤坏死因子-α（TNF-α）和钥孔戚血蓝蛋白（KLH）对细胞进行脉冲处理。在第9天收集非贴壁细胞，并将细胞注入腹股沟淋巴结。每位患者每周接受4次1-10×10⁶个细胞的治疗。
结果
所有患者对免疫治疗耐受性良好，无明显毒性。DC疫苗接种在10例患者中的7例中诱导了针对KLH的迟发型超敏反应（DTH）。在1例患者中，两个肝肿瘤之一（位于第7段，直径13mm）在8次免疫治疗后，大小缩小至7mm，计算机断层扫描检查显示有坏死改变。在2例患者中，接种疫苗后血清肿瘤标志物水平下降。
结论
目前的临床试验表明，用TL脉冲DC进行免疫治疗在不可切除的PLC患者中是可行的，且无任何毒性。通过修改治疗方案，有望进一步改善免疫治疗的临床效果。
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