Höltl L, Rieser C, Papesh C, Ramoner R, Herold M, Klocker H, Radmayr C, Stenzl A, Bartsch G, Thurnher M
Department of Urology, University of Innsbruck, Austria.
J Urol. 1999 Mar;161(3):777-82.
Dendritic cells are the most potent stimulators of immune responses including antitumor responses. We performed a pilot study of cultured antigen loaded dendritic cells in patients with metastatic renal cell carcinoma.
Dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 5 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Day 5 dendritic cells were loaded with cell lysate from cultured autologous tumor cells and with the immunogenic protein keyhole-limpet hemocyanin (KLH) which serves as a helper antigen and as a tracer molecule. During the antigen pulse dendritic cells were activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Dendritic cells were administered by 3 intravenous infusions at monthly intervals. Cellular and humoral immune responses to KLH and cell lysate were measured in vitro before and after the vaccinations.
Preparation of 12 dendritic cell vaccines from patients with advanced renal cell carcinoma was successful. Treatment with fully activated CD83+ dendritic cells was well tolerated with moderate fever as the only side effect. Potent immunological responses to KLH and, most importantly, against cell lysate could be measured in vitro after the vaccinations.
Our data demonstrate that a dendritic cell based vaccine can induce antigen specific immunity in patients with metastatic renal cell carcinoma. Dendritic cell based immunotherapy represents a feasible, well tolerated and promising new approach for the treatment of advanced renal cell carcinoma.
树突状细胞是包括抗肿瘤反应在内的免疫反应的最有效刺激物。我们对转移性肾细胞癌患者进行了一项关于培养的负载抗原的树突状细胞的初步研究。
通过在粒细胞-巨噬细胞集落刺激因子和白细胞介素-4存在的情况下，将外周血中的塑料贴壁单核细胞培养5天来获得树突状细胞。第5天的树突状细胞用培养的自体肿瘤细胞的细胞裂解物以及作为辅助抗原和示踪分子的免疫原性蛋白钥孔戚血蓝蛋白（KLH）进行负载。在抗原脉冲期间，树突状细胞用肿瘤坏死因子-α和前列腺素E2的组合进行激活。树突状细胞通过每月一次的3次静脉输注给药。在接种疫苗前后体外测量对KLH和细胞裂解物的细胞免疫和体液免疫反应。
从晚期肾细胞癌患者制备12种树突状细胞疫苗成功。用完全活化的CD83 +树突状细胞进行治疗耐受性良好，唯一的副作用是中度发热。接种疫苗后在体外可测量到对KLH以及最重要的是对细胞裂解物的强烈免疫反应。
我们的数据表明，基于树突状细胞的疫苗可以在转移性肾细胞癌患者中诱导抗原特异性免疫。基于树突状细胞的免疫疗法是治疗晚期肾细胞癌的一种可行、耐受性良好且有前景的新方法。
