Immunotherapy using fusions of autologous dendritic cells and tumor cells showed effective clinical response in a patient with advanced gastric carcinoma

被引:45
作者
Homma, S
Matai, K
Irie, M
Ohno, T
Kufe, D
Toda, G
机构
[1] Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Minato Ku, Tokyo 1058461, Japan
[2] Jikei Univ, Sch Med, Dept Surg, Tokyo, Japan
[3] Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med, Tokyo, Japan
[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA
关键词
dendritic cells; gastric carcinoma; immunotherapy; cell fusion; cell therapy;
D O I
10.1007/s00535-002-1183-3
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Immunotherapy using, tumor antigen-loaded dendritic cells is a new approach for the treatment of various types of malignant tumors. Here, we describe a patient with advanced gastric carcinoma who received immunotherapy using fused autologous dendritic cells and carcinoma cells (fusions) and showed effective clinical responses to the treatment. A 74-year-old man showed massive ascitic effusion due to peritonitis carcinomatosa after surgical operation for gastric carcinoma. A gastric carcinoma cell line was established from the patient's tumor tissue. Dendritic cells were obtained by cultivation of the adherent cell fraction of the patient's peripheral blood mononuclear cells (PBMCs) with granulocyte macrophage-colony stimulating factor, interleukin-4, and tumor necrosis factor-alpha. The cells were mixed with irradiated tumor cells and treated with 50% polyethyleneglycol (PEG) for the generation of fusions, as described previously. The PEG-treated cells were injected subcutaneously every 2 weeks. Low-grade fever was observed after the first and second treatments. After the third treatment, ascitic effusion and leg edema decreased markedly, without any other treatments. Serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 decreased to levels lower than those at the initiation of treatment. PBMCs collected after the fifth treatment elicited cytotoxic activity against autologous tumor cells. Although treatment was continued in the same way, recurrence of the disease was observed about 5 months after the start of the treatment. This is the first report of immunotherapy utilizing fusions of autologous dendritic cells and tumor cells resulting in effective clinical responses in advanced gastric carcinoma, without severe adverse effects.
引用
收藏
页码:989 / 994
页数:6
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