《中国康复理论与实践》 ›› 2007, Vol. 13 ›› Issue (03): 252-254.

• 基础研究 • 上一篇    下一篇

混合性热休克蛋白/肽疫苗与白细胞介素-12联合诱导特异性细胞毒T淋巴细胞产生的实验研究

宋舸; 袁玫; 崔雪梅; 眭翔; 赵斌; 卢世璧   

  1. 中国人民解放军总医院骨科研究所,北京市 100853
  • 收稿日期:2006-12-21 出版日期:2007-03-01 发布日期:2007-03-01

Combined Therapy with Mixed Heat Shock Protein/Peptide Vaccine and Interleukin-12 Results in Enhanced Antitumor Effects

SONG Ge, YUAN Mei, CUI Xue-mei, et al   

  1. Institute of Orthopaedics, General Hospital of PLA, Beijing 100853, China
  • Received:2006-12-21 Published:2007-03-01 Online:2007-03-01

摘要: 目的研究肿瘤组织来源混合热休克蛋白(mHSPs)/肽疫苗诱导产生特异性细胞毒性T淋巴细胞(CTL)的作用及其抗肿瘤免疫效应,为应用其治疗人类恶性肿瘤提供实验依据。方法利用细胞培养、流式细胞技术、蛋白质的分离纯化技术、电泳技术、Westernblot检测方法、T淋巴细胞的诱导及体外扩增、乳酸脱氢酶法等,测定肿瘤多肽复合物诱导活化小鼠体内CTL杀伤效应。结果mHSPS免疫组和mHSPs+Cy+IL-12免疫组体外诱生的CTL反应活性均比对照组的CTL活性有所升高,尤其mH-SPs+Cy+IL-12免疫组升高明显,且随效靶比的上升而上升;与正常小鼠(CD4+46%、CD8+18%)比较,对照组、mHSPs免疫组及mHSPs+Cy+IL-12免疫组小鼠CD4+亚群的比例分别为38%、46%、54%。CD8+亚群的比例分别为26%、22%、16%。结论混合热休克蛋白/肽可诱发强大的抗肿瘤免疫效应,当与IL-12、低剂量Cy者联合应用后免疫功能增强最为明显。

关键词: S180肉瘤, 肿瘤, 免疫治疗, 混合热休克蛋白/肽, 细胞毒T淋巴细胞, 疫苗

Abstract: Objective To investigate the antitumor immunity induced by tumor derived mixed heat shock protein/peptide(mHSPs),interleukin-12(IL-12)and Cyclophosphamide(Cy).MethodsPurified mixed HSP was prepared from tumor by S180 protein extraction and purification,SDS-PAGE,Western blot and animal experiment were applied for mixed HSPs analysis.ResultsThe proliferation of cytotoxic T lymphocyte(CTL)cocultured in the mHSPs+Cy+IL-12 group was significantly remarkable and the content of CD8+ CTLs was significantly more in comparison with the other groups(P<0.01).To the tumor bearing mice,mHSPs+Cy+IL-12 group showed partial therapeutic efficacy,the averaged survival period was over 60 d,and 90% of the mice in this group got long period tumor free survival(>90d),obvious difference(P<0.05)from the other groups.ConclusionTumor derived mixed HSPs can induce powerful antitumor immune efficacy and show favorable therapeutic efficacy.

Key words: sarcoma-180, neoplasm, immunotherapy, mixed heat shock proteins/peptide complexes, cytotoxic T lymphocyte (CTL), vaccine