两种前列腺癌多肽负载的树突状细胞治疗晚期前列腺癌的临床初步研究  

A primary study of immunotherapy with twoprostate peptide pulsed dendritic cells in advanced prostate cancer patients

作　　者：邹青[1] 须霆[1] 杨尔炘[1] 汪仪俊[1] 王亚军[1] 芮清[1] 赖娅娜[1] 

机构地区：[1]江苏省肿瘤医院普外科,南京210041

出　　处：《临床泌尿外科杂志》2008年第9期649-652,666,共5页Journal of Clinical Urology

摘　　要：目的:探讨前列腺癌多肽PSMA-P1及PSMA-P2负载患者自体的树突状细胞治疗晚期前列腺癌的临床近期疗效和毒副反应。方法:选择8例非激素依赖型且HLA-A2阳性的晚期前列腺癌患者,分离出外周血中单个核细胞(PBMC),用重组人粒细胞-噬细胞集落刺激因子(rhGM-CSF)和白细胞介素4(rhIL-4)体外诱导树突状细胞(Dendritic cells,DC),培养至第5天经催熟24h后,以PSM-P1多肽与PSM-P2多肽片段(HLA-A2阳性)进行负载。将成熟DC经皮内注射,观察患者的临床疗效,指标有客观缓解率、临床收益率和毒副反应。结果:8例前列腺癌患者血液中Th1细胞因子水平(IL-2/IL-12/IFN-r/TNF-a)明显升高(P<0.05);3例患者肿瘤标志物PSA降低,2例平稳,1例升高。1例患者胸腔积液消失。3例早期患者随访10～13个月,其中2例目前病情稳定,1例死于其他并发症。主要毒副反应为乏力及注射部位处轻微疼痛。结论:前列腺癌术后行多肽负载的DC瘤苗治疗,可改善患者的生活质量和免疫功能,且不良反应少,可明显控制PSA升高,缓解病情,值得推广应用。Objective： To explore the short term clinical efficacy and security of infusions of dendritic cells pulsed with PSMA P1 and PSMA P2 in patients with advanced prostate cancer. Methods： All patients suffered from hormone refractory prostate cancer （HRPC） and were confirmed to be HLA A2 positive. Peripheral blood mononuclear cells（PBMC） were isolated from all patients, and cultured with granulocyte macrophage colony stimulating factor （GMCSF）. interleukin 1 （IL-4） for 5 days. matured with TNF-α and PGE（2） for 2 days. Prior to treatment. DCs were exogenously pulsed witb peptide via incubation with PSM P1 and PSM P2 for 24 h. Objec tire response rate, clinical benefit rate and toxiclties were observed after infusions. Results：Immunological effects were tested in 8 castrated prostatic cancer patients infused with DC pulsed with PSMA PI or PSMA P2, respec tively. SpecificThl cytokinelevers （IL-2 IL 12/IFN-γ/TNF-α） obviously increased after treatment （P〈0.05）. 3 patients PSA levels dropped, 2 patients remained and 1 patient increased. The hydrothorax disappeared in 1 patient. 3 early patients were followed up after being discharged（ 10-13 months）, 2 patients showed stable disease throughout the study period, 1 easedied of other complications. Main adverse effects were slightly rash and rnus cle fatigue. Conclusions：Prostate peptides pulsed DCs Immunotherapy vaccination show great promise to improve the life qualityand boost specific Th1 immune responses, providea novel strategy for safe and effective treatment for prostate cancer.

关 键 词：前列腺癌 树突状细胞 多肽 免疫治疗 

分 类 号：R737.25[医药卫生—肿瘤]