Pecher Gabriele, Häring Arnt, Kaiser Lothar, Thiel Eckhard
Departmet of Hematology and Oncology, Free University of Berlin, Universitätsklinikum Benjamin Franklin, Berlin, Germany.
Cancer Immunol Immunother. 2002 Dec;51(11-12):669-73. doi: 10.1007/s00262-002-0317-z. Epub 2002 Oct 19.
Dendritic cells (DC) derived from peripheral blood monocytes are currently being investigated in clinical trials for their role in stimulating the immune system. We performed a phase I/II clinical trial using human autologous DC transfected with cDNA of the human tumor antigen mucin (MUC1) as a vaccine in 10 patients with advanced breast, pancreatic or papillary cancer. After liposomal transfection, flow cytometry testing showed that 2% to 53% of the DC expressed mucin epitopes. Patients were immunized two or three times with 1 million transfected DC injected subcutaneously (s.c.). A vaccine-specific delayed-type hypersensitivity (DTH) reaction was observed in 3 out of 10 patients. After vaccination, 4 patients showed a 2- to 10-fold increase in the frequency of mucin-specific interferon-gamma (IFN-gamma)-secreting CD8+ T cells. We demonstrated the feasibility and safety of a vaccine consisting of autologous gene-transfected DC, and that immunologic responses could be induced even in patients with pretreated and advanced disease.
目前，来源于外周血单核细胞的树突状细胞（DC）在刺激免疫系统方面的作用正在临床试验中进行研究。我们对10例晚期乳腺癌、胰腺癌或乳头状癌患者进行了I/II期临床试验，使用转染了人类肿瘤抗原粘蛋白（MUC1）cDNA的人自体DC作为疫苗。脂质体转染后，流式细胞术检测显示2%至53%的DC表达粘蛋白表位。患者皮下注射100万个转染的DC，进行2或3次免疫。10例患者中有3例观察到疫苗特异性迟发型超敏反应（DTH）。接种疫苗后，4例患者分泌粘蛋白特异性干扰素-γ（IFN-γ）的CD8+T细胞频率增加了2至10倍。我们证明了由自体基因转染DC组成的疫苗的可行性和安全性，并且即使在经过预处理的晚期疾病患者中也能诱导免疫反应。
