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树突状细胞治疗大鼠肝癌的实验研究 被引量:3

The experimental research of rat hepatoma immunotherapy using dendritic cells loaded with tumor antigens
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摘要 目的 通过负载癌抗原的树突状细胞 (DC)治疗大鼠原发性肝癌 (HCC)模型的实验 ,探讨其临床生物治疗的可行性。方法 用大鼠HCC细胞株CBRH 7919细胞匀浆粗提物 ,刺激Wistar大鼠骨髓衍化的DC ,按不同途径 (静脉、腹腔、癌内注射 )、低中高不同剂量 (10 6、10 7、10 8)静脉注射多次治疗CBRH 7919接种的大鼠HCC模型 ,并设预治疗组、细胞因子加CBRH 7919细胞匀浆粗提物治疗组和生理盐水组作对照 ,用 χ2 检验比较其疗效和生存期。结果 比较各组获得长期生存 (生存大于 10 0d)的大鼠数 ,细胞因子加CBRH 7919细胞匀浆粗提物治疗组、腹腔治疗组及高剂量静脉治疗组与生理盐水组比较无显著意义 (P >0 0 5 ) ;中低剂量静脉治疗组、预治疗组及癌内注射组与生理盐水组比较有显著意义 (P <0 0 5、P <0 0 0 1、P <0 0 0 1和P <0 0 1;预治疗组成癌率与其余各组相比有显著意义 (P <0 0 0 1)。结论 中、低剂量负载癌抗原DC经静脉和癌内多次注射 ,对大鼠HCC有一定的疗效 ,并能有效地抵抗HCC细胞的再接种 。 Objectives To study the feasibility of hepatocellular carcinoma immunotherapy with dendritic cells loaded with tumor antigens and to provide the fundation for its clinical application. Methods [ Rat hepatocellular carcinoma models were treated with dendritic cells derived from rat bone marrow mononuclear cells pulsed with CBRH 7919 cellular homogenate extract by different way (administrated via tail vein, abdominal cavity, intratumoral) and with different cell quantity (10 6,10 7,10 8) via vein. The tumorbearing rats in control groups were given NS and CBRH 7919 cellular homogenate extract and cytokines separately. The rats in another group which have been pre treated with rat bone marrow derived syngeneic dendritic cells pulsed with CBRH 7919 cellular homogenate extract were challenged with 1×10 6 CBRH 7919. The curative effect and the survival time of rats in each group was observed and compared with the control groups by χ 2 test.[ Results] The survival rates of the rats in intravenous group (10 8) and in abdominal cavity group were not significantly different from control groups (compared with control group, P >0 05 by χ 2 test). The rats in intravenous groups (10 6,10 7) and in intratumoral group had significant prolonged survival (compared with control group, P <0 05, P <0 001 and P <0 01 respectively, by χ 2 test). Rats in pre treated group did not develop tumors after being challenged with 1×10 6 CBRH 7919 and had a longer survival(compared with control group, P <0 001, by χ 2 test).[WT5”HZ] Conclusions [WT5”BZ] The immunotherapy of hepatocellular carcinoma rats with middle and low dose dendritic cells pulsed with cellular homogenate extract is effective relatively via vein and intratumor repeatedly. Dendritic cells loaded with tumor antigens can resist the challenge of reinoculability of hepatoma cells effectively. These results suggest that hepatocellular carcinoma immunotherapy with dendritic cells loaded with tumoral antigens has potential feasibility to be applied in clinical settings.
出处 《中华普通外科杂志》 CSCD 北大核心 2001年第4期228-230,共3页 Chinese Journal of General Surgery
关键词 树突状细胞 肝细胞癌 大鼠 动物模型 Dendritic cells Carcinoma, hepatocellular
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参考文献2

  • 1Eggert AAO,Schreurs MWJ,Boerman OC,et al.Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration[].Cancer Research.1999
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  • 2郝葆青,刘鲁蜀,张晓东.DNA疫苗的研究与应用前景[J].华西医学,2005,20(1):197-198. 被引量:6
  • 3罗晨,李官成.DNA疫苗与肿瘤免疫治疗[J].国际病理科学与临床杂志,2006,26(4):333-335. 被引量:5
  • 4Yang JM,Peng ZH,Si H. KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97H cells in vitro and in animal models[J].{H}Liver International,2008.132-139.
  • 5Dranoff G. GM-CSF-secreting melanoma vaccines[J].{H}ONCOGENE,2003,(20):3188-3319.
  • 6Tabi Z,Man S. Challenges for cancer vaccine development[J].{H}Advanced Drug Delivery Reviews,2006,(08):902-915.
  • 7Corbiere V,Nicolay H,Russo V. Identification of a MAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-B* 5701 tumors[J].{H}Tissue Antigens,2004,(05):453-457.
  • 8Ye J,Chen GS,Song HP. Heat shock protein 70/MAGE-1 tumor vaccine can enhance the potency of MAGE 1specific cellular immune responsesin vivo[J].Cancer Imrnunol Immunother,2004,(09):825-834.
  • 9Ma JH,Sui YF,Ye J. Heat shock protein 70/MAGE-3 fusion protein vaccine can enhance cellular and humoral immune responses to MAGE-3 in vivo[J].{H}Cancer Immunology lmmunotherapy,2005,(09):907-914.
  • 10Li ZS,Yang XW,Chen Z. In vivo tumor transfection with superantigen and CD80 induces systemic immunity without tolerance and prolongs survival in mice with hepatocellular carcinoma[J].{H}CANCER BIOLOGY & THERAPY,2004,(07):660-666.

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