Höltl Lorenz, Ramoner Reinhold, Zelle-Rieser Claudia, Gander Hubert, Putz Thomas, Papesh Christine, Nussbaumer Walter, Falkensammer Claudia, Bartsch Georg, Thurnher Martin
Department of Urology/kompetenzzentrum medizin tirol, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Cancer Immunol Immunother. 2005 Jul;54(7):663-70. doi: 10.1007/s00262-004-0629-2. Epub 2004 Dec 17.
In this phase I/II study, we evaluated the feasibility, safety and efficacy of allogeneic dendritic cells (DCs) with or without cyclophosphamide in the treatment of patients with metastatic renal cell carcinoma (RCC). Immunomagnetic beads were used to isolate CD14(+) monocytes from healthy donor leukapheresis products, and CD83(+) antigen-pulsed monocyte-derived DCs (moDCs) loaded with tumor lysate and keyhole limpet hemocyanin (KLH) were generated. Twelve patients were treated with allogeneic moDCs alone, while ten patients also received cyclophosphamide on days 4 and 3 prior to vaccination. Of the 22 patients enrolled, 20 received full treatment consisting of at least three vaccinations at monthly intervals. Two mixed responses with substantial tumor regression were observed. In 3 patients, disease stabilization occurred, in 13 patients disease progressed and 4 patients were lost to follow-up. Overall, immune responses against KLH and tumor lysate were weak or absent; however, the strongest increases in antigen-independent and KLH-specific responses were observed in the 2 patients with mixed responses. In addition, 1 of them showed a substantial increase in oncofetal antigen (OFA)-specific IFN-gamma production. Importantly, the 2 mixed responders and 1 patient with stable disease belonged to the cyclophosphamide group. Median overall survival in the cyclophosphamide group was 23.2 and 20.3 months in the group that received allogeneic moDCs alone. Allogeneic immunotherapy with moDCs is feasible and well tolerated. However, the immunogenicity of allogeneic moDCs is clearly less pronounced than that of autologous moDC immunotherapy. Cyclophosphamide may have the capacity to augment DC-induced antitumor immunity.
在这项I/II期研究中，我们评估了异体树突状细胞（DCs）联合或不联合环磷酰胺治疗转移性肾细胞癌（RCC）患者的可行性、安全性和疗效。使用免疫磁珠从健康供体白细胞分离产物中分离CD14(+)单核细胞，并生成负载肿瘤裂解物和钥孔戚血蓝蛋白（KLH）的CD83(+)抗原脉冲单核细胞衍生DCs（moDCs）。12例患者仅接受异体moDCs治疗，而10例患者在接种前第4天和第3天还接受了环磷酰胺治疗。在入组的22例患者中，20例接受了完整治疗，包括至少每间隔一个月进行三次接种。观察到2例出现显著肿瘤消退的混合反应。3例患者病情稳定，13例患者病情进展，4例患者失访。总体而言，针对KLH和肿瘤裂解物的免疫反应较弱或未出现；然而，在2例有混合反应的患者中观察到非抗原依赖性和KLH特异性反应的最强增加。此外，其中1例患者癌胚抗原（OFA）特异性干扰素-γ产生显著增加。重要的是，2例有混合反应的患者和1例病情稳定的患者属于环磷酰胺组。环磷酰胺组的中位总生存期为23.2个月，仅接受异体moDCs治疗的组为20.3个月。异体moDCs免疫治疗是可行的且耐受性良好。然而，异体moDCs的免疫原性明显低于自体moDC免疫治疗。环磷酰胺可能有增强DC诱导的抗肿瘤免疫的能力。
