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B7-1与CD40L在淋巴瘤免疫治疗中的协同作用 被引量:4

Synergetic Effect of B7-1 and CD40L in the Immunotherapy for Lymphoma
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摘要 为了研究B7-1与CD40L共刺激途径在淋巴瘤的免疫治疗中的作用,探讨治疗淋巴瘤疫苗有效的作用方式,将A20淋巴瘤细胞株接种在BALB/c小鼠身上以构建荷瘤小鼠模型,将B7-1与CD40L表达载体单独或联合导入肿瘤内,以PBS和空载体作为对照,观察肿瘤生长的情况;应用肿瘤病理切片和HE染色技术观察肿瘤组织形态及淋巴细胞浸润情况,采用CCK-8试剂盒检测荷瘤小鼠脾CTL杀伤效应。结果显示,瘤内注射B7-1或CD40L表达载体可导致肿瘤生长延缓或体积缩小,两者联合注射较对照组和单独注射组的肿瘤消退效应明显增强。肿瘤形态学观察表明,治疗小鼠肿瘤局部有炎性细胞浸润并伴有大面积的坏死,肿瘤局限化;CCK8试剂盒检测显示小鼠脾CTL杀伤能力增强。结论:B7-1与CD40L疫苗对淋巴瘤具有治疗效应,两者联合治疗的效果优于单一治疗。质粒载体瘤内注射可作为一种安全有效的肿瘤疫苗作用方式。 The aim of study was to investigate the synergetic effect of B7-1 and CD40L co-stimulating pathway in the immunotherapy for lymphoma and to explore the effective manner of tumor vaccine for treating lymphoma, The lymphoma cell line A20 cells were inoculated into BALB/c mice as to establish A20-bearing mice model, the BT-1 and CD40L expression vector were alone or in combination directly injected into lymphoma of mice model, the PBS, vector pcDM8 and pcDNA3.1 were selected as controls so as to observe tumor growth. The pathological section and HE staining of tumor tissue were performed to observe the histological characteristics and the cell infiltration of lymphoma, the CCK-8 detection kit was used to analysis the splenic CTL cytotoxicity. The results showed that the intratumor injection of B7-1 and CD40L resulted in reduction of tumor size. Morphological observation of tumor revealed inflammatory cell infiltration in the tumors, massive necrosis and localization of tumor. CCK-8 kit detection indicated significant enhancement of splenic CTL cytotoxicity, the effect of B7-1 combined with CD40L was stronger than that of B7-1 or CD40L alone. It is concluded that B7-1 and CD40L show immunotherapeutic effect on lymphoma, and the effect becomes stronger when they are combined in treating lymphorna. Meanwhile, the intratumor injection may be considered as a safe and effective way for tumor vaccine.
出处 《中国实验血液学杂志》 CAS CSCD 2008年第2期317-321,共5页 Journal of Experimental Hematology
基金 国家自然科学基金,编号30371579
关键词 淋巴瘤 B7—1 CD40L 基因治疗 肿瘤疫苗 lymphoma B7 CD40L gene-therapy tumor vaccine
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参考文献12

  • 1Zhou ZF, Peretz Y, Chang Y, et al.Intramuscular gene transfer of soluble B7. 1/IgG( 1 ) fusion cDNA induces potent antitumor immunity as an adjuvant for DNA vaccination. Cancer Gene Ther, 2003 ; 10 : 491 - 499
  • 2Stopeck AT , Jones A , Hersh EM , et al, Phase Ⅱ study of direct intralesional gene transfer of allovectin 27, an HLA-B7/beta 2-microglobulin DNA-liposome complex , in patients with metastatic melanoma. Clin Cancer Res, 2001 ; 7 :2285 - 2291
  • 3Vasilevko V , Ghochikyan A , Sadzikava N , et al.Immunization with a vaccine that combines the expression of MUC1 and B7 costimulatory molecules prolongs the survival of mice and delays the appearance of mouse mammary tumors. Clin Exp Metastasis, 2003 ; 20:489 -498
  • 4克晓燕,John Gribben,王晶,王德炳.B7-1与B7-2对调节人IL-2基因的转录因子NF-κB和AP-1的相同作用[J].中国实验血液学杂志,2002,10(6):512-518. 被引量:5
  • 5贾丽萍,克晓燕.转染B7-1基因的Raji和Jurkat细胞诱导细胞因子mRNA表达的研究[J].中国实验血液学杂志,2002,10(4):322-326. 被引量:3
  • 6Morioka J , Kajiwara K, Yoshikawa K, et al. Vaccine therapy for murine glioma using tumor cells genetically modified to express B7.1. Neurosurgery, 2004; 54:182 - 189
  • 7Tsuji H, Kawaguchi S, Wada T, et al. Adenovirus-mediated in vivo B7-1 gene transfer induces anti-tumor immunity against pre-established primary tumor and pulmonary metastasis of rat osteosarcoma. Cancer Gene Ther, 2002 ; 9:747 - 755
  • 8Raez LE, Cassileth PA , Schlesselman JJ , et al.Allogeneic vaccination with a B7. 1 HLA-A gene-modified adenocarcinoma cell line in patients with advanced non-small-cell lung cancer. J Clin Oncol, 2004 ; 22 : 2800 - 2807
  • 9Kimura T, Ohashi T, Kikuchi T, et al.Antitumor immunity against bladder cancer induced by ex vivo expression of CD40 ligand gene using retrovirus vector. Cancer Gene Therapy, 2003 ;10 : 833 - 839
  • 10Briones J, Timmerman J, Levy R. in vivo antitumor effect of CD40L-transduced tumor cells as a vaccine for B-cell lymphomal. Cancer Res, 2002 ; 62 : 3195 - 3199

二级参考文献10

  • 1Boussiotis VA, Freeman GJ, Gray G, et al. B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance. J Exp Med, 1993; 178:1753- 1763
  • 2Bretscher P. The two-signal model of lymphocyte activation twenty one years later. Immunol Today, 1992; 13:74-76
  • 3Freeman GJ, Boussiotis VA, Anumanthan A, et al. B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7 1 preferentially costimulates the initial production of IL-4. Immunity, 1995; 2:523- 532
  • 4Mueller DL, Jenkine MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway de termines the outcome of T cell antigen receptor occupancy. AnnuRev Immunol, 1989; 7:445 - 480
  • 5Kuchroo VK, Martin CA, Greer JM, et al. Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-spe cific T cell clones to mediate experimental allergic encephalomyelitis. J Immunol, 1993; 151:4371-4382
  • 6Simon AK, Seipelt E, Sieper J. Divergent T-cell cytokine patterns in inflammatory arthritis. Proc Natl Acad Sci USA, 1994; 91:8562- 8566
  • 7J@萨姆布鲁克,EF弗里奇,T曼尼阿蒂斩主编(金冬雁,黎孟枫等译).分子克隆实验指南.第一版.北京:科学出版社,1992:24-27,55-56
  • 8Heuer JG, Tucker-McClung C, Gonin R, et al. Retrovirus-mediated gene transfer of B7-1 and MHC class Ⅱ converts a poorly immunogenic neuroblastoma into a highly immunogenic one. Hum Gene Ther, 1996; 7:2059- 2068
  • 9Paliard X, De Waal Malefijt R, Yssel H, et al. Simultaneous pro ductionof IL-2, IL-4, and IFN-γ by activated human CD4+ and CD8+ T cell clones. J Immunol, 1988; 141:849-855
  • 10王晶,克晓燕,贾丽萍.抗B7分子抗体诱导T细胞免疫耐受研究[J].中华血液学杂志,2002,23(7):341-344. 被引量:3

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