Oosterwijk-Wakka Jeannette C, Tiemessen Dorien M, Bleumer Ivar, de Vries I Jolanda M, Jongmans Wim, Adema Gosse J, Debruyne Frans M J, de Mulder Pieter H, Oosterwijk Egbert, Mulders Peter F A
Experimental Urology, University Medical Center, 6500 HB Nijmegen, The Netherlands.
J Immunother. 2002 Nov-Dec;25(6):500-8. doi: 10.1097/00002371-200211000-00006.
Dendritic cells (DC) have been recognized as the most potent antigen presenting cells (APC) of the immune system. We performed a phase 1 study in twelve patients with metastatic renal cell carcinoma (RCC) using autologous immature DC loaded with autologous tumorlysate (TuLy) as a vaccine based on our earlier in vitro observations that such DC can activate tumor-specific cytotoxic T-lymphocytes. The treatment was combined with low-dose interleukin (IL)-2, as this has shown benefit in DC-based therapies. Patients received three intradermal vaccinations at two weekly intervals, and, after each vaccination, IL-2 was administered for 5 consecutive days. In six patients, keyhole-limpet hemocyanin (KLH) was added to the DC culture for immunologic monitoring purposes. In general, DC phenotype was CD14(low), CD86(high), CD40(high), CD80(low), and CD83(low). We noticed that the number of CD14+ cultured DC increased during treatment. Nevertheless, ovalbumin uptake remained high, underlining that these cells were still functional immature DC. The vaccine was able to elicit cellular anti-KLH responses, emphasizing the ability of the injected DC to mount an immunologic response. However, proliferative responses against TuLy were not detected, and humoral responses against TuLy or KLH were absent. Objective clinical responses were not observed, but extended stable disease was noted. The absence of cellular, humoral, or clinical antitumor responses suggests that the vaccination strategy with immature DC has little benefit for patients with advanced RCC. Nevertheless, this study shows the feasibility of a completely autologous DC and tissue culture methodology for the generation of TuLy pulsed DC.
树突状细胞（DC）已被公认为免疫系统中最强大的抗原呈递细胞（APC）。基于我们早期的体外观察结果，即此类DC可激活肿瘤特异性细胞毒性T淋巴细胞，我们对12例转移性肾细胞癌（RCC）患者进行了1期研究，使用负载自体肿瘤裂解物（TuLy）的自体未成熟DC作为疫苗。该治疗与低剂量白细胞介素（IL）-2联合使用，因为这已在基于DC的治疗中显示出益处。患者每隔一周接受三次皮内接种疫苗，每次接种疫苗后，连续5天给予IL-2。在6例患者中，为了免疫监测目的，将匙孔血蓝蛋白（KLH）添加到DC培养物中。一般来说，DC表型为CD14（低）、CD86（高）、CD40（高）、CD80（低）和CD83（低）。我们注意到治疗期间CD14 +培养的DC数量增加。然而，卵清蛋白摄取仍然很高，这表明这些细胞仍然是功能未成熟的DC。该疫苗能够引发针对KLH的细胞免疫反应，强调了注射的DC引发免疫反应的能力。然而，未检测到针对TuLy的增殖反应，也未检测到针对TuLy或KLH的体液反应。未观察到客观临床反应，但注意到疾病稳定期延长。细胞、体液或临床抗肿瘤反应的缺失表明，用未成熟DC进行疫苗接种策略对晚期RCC患者益处不大。尽管如此，本研究表明了一种完全自体DC和组织培养方法用于生成TuLy脉冲DC的可行性。
