Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients.
Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients.
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DOI：
10.1158/1078-0432.ccr-08-3240
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发表时间：
2009-08-01
期刊：
影响因子：
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通讯作者：
Ernstoff MS
中科院分区：
文献类型：
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作者：
Schwaab T;Schwarzer A;Wolf B;Crocenzi TS;Seigne JD;Crosby NA;Cole BF;Fisher JL;Uhlenhake JC;Mellinger D;Foster C;Szczepiorkowski ZM;Webber SM;Schned AR;Harris RD;Barth RJ Jr;Heaney JA;Noelle RJ;Ernstoff MS
目的探讨树突状细胞（DC）疫苗联合白细胞介素（IL）-2和IFN-α 2a治疗转移性肾癌的临床疗效和免疫学效果。18例知情同意且合格的患者接受了治疗。将外周血单核细胞离体培养成成熟DC并加载自体肿瘤裂解物。治疗包括5个周期的DC结内接种（1 × 107个细胞/1 mL乳酸林格氏溶液）、5天连续静脉内输注IL-2（18 MiU/m2）和3次皮下注射（100 ml）。IFN-α 2a（6 MiU）隔日注射。采用实体瘤疗效评价标准进行疾病评估。相关免疫学终点包括外周血淋巴细胞表型和功能以及外周血抗肾癌抗体和细胞因子水平。所有患者均接受2 - 5个治疗周期。毒性包括已知和预期的细胞因子副作用。总体客观临床缓解率为50%，其中3例完全缓解。所有患者的中位进展时间为8个月，中位生存期尚未达到（中位随访时间为37+个月）。观察到相关免疫学终点的治疗相关变化，并且循环CD 4 + T调节细胞水平与结果有很强的相关性。前IP-10血清水平接近预测结果的意义。本试验中观察到的临床和免疫学应答表明DC疫苗接种和细胞因子治疗之间存在相互作用。我们的数据支持这一假设，即炎症，调节和血管生成途径的调制是必要的，以优化肾细胞癌患者的治疗效果。有必要进一步探讨这一办法。
To evaluate the clinical and immunologic outcomes of DC (dendritic cell) vaccine with interleukin (IL)-2 and IFN-α 2a in metastatic renal cell carcinoma patients. Eighteen consented and eligible patients were treated. Peripheral blood monocytes were cultured ex vivo into mature DCs and loaded with autologous tumor lysate. Treatment consisted of five cycles of intranodal vaccination of DCs (1 × 107 cells/1 mL Lactated Ringer’s solution), 5-day continuous i.v. infusion of IL-2 (18MiU/m2), and three s.c. injections of IFN-α 2a (6MiU) every other day. Response Evaluation Criteria in Solid Tumors criteria were used for disease assessment. Correlative immunologic end points included peripheral blood lymphocyte cell phenotype and function as well as peripheral blood anti–renal cell carcinoma antibody and cytokine levels. All patients received between two and five treatment cycles. Toxicities consisted of known and expected cytokine side effects. Overall objective clinical response rate was 50% with three complete responses. Median time to progression for all patients was 8 months, and median survival has not been reached (median follow up of 37+ months). Treatment-related changes in correlative immunologic end points were noted and the level of circulating CD4+ T regulatory cells had a strong association with outcome. Pre–IP-10 serum levels approached significance for predicting outcome. The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted.