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CD20单克隆抗体的制备及治疗B细胞淋巴瘤研究进展

Preparation of Anti-human CD20 Monoclonal Antibody and Recent Advance in Anti-CD20 Monoclonal Antibody Therapy in B-cell Lymphoma
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摘要 目的:制备CD20的单克隆抗体(mAb),并探讨对治疗B细胞淋巴瘤的作用机制。方法:构建重组表达质粒pGEX-4T-1-CD20和pET-32a-CD20。以融合蛋白CD20-GST为免疫源免疫BALB/c雌性小鼠制备(mAb)。结果:CD20-GST和CD20-His蛋白在大肠杆菌中可高效表达,经纯化后可获得高纯度的CD20蛋白。结论:成功制备高纯度CD20蛋白并以此为抗原制备了1株能够稳定分泌抗人CD20的鼠单mAb的杂交瘤细胞株BD11F4。临床试验结果表明,抗CD20单克隆抗体既可单独应用,亦可作为放射性同位素或细胞毒制剂的载体,其疗效显著,且使用安全,副反应小。许多研究报道已阐明了抗CD20单克隆抗体治疗B细胞淋巴瘤的几种可能的效应机制。目前,人们正致力于探索一些新的治疗策略以期提高这种疗法的特异性,减少其非特异性的毒副作用。 Objective: To prepare its monoclonal antibody and discuss on mechanism of B-cell lymphoma.Methods: The CD20 gene was amplified from human histoleucocyte by RT-PCP, and were cloned into expression vectors and generate pGEX-4T-1-CD20(CD20-GST) and pET-32a-CD20 (CD20-His). Immunized the BALB/c mice with purified CD20-GST to prepare the monodonal antibody.Results:CD20-GST and CD20-His were highly expressed in E-coli and got the CD20 protein with high purity.Conclusions:We prepared the CD20 fusion protein with high purity. The mAb against CD20 with high titer and specificity has been obtained, which lays the foundation for investigation of CD20 function and diagnosis and therapy of non-Hodgkin lymphonla(NHL). The results of clinical trials had showed that antiCD20 monoclonalantibodies , which could be utilized in either unmodified form or as carrier for radioisotopes or cytotoxic agents ,have significant effects and can be administ rated safely with minimum side effects.
作者 孙宇 褚晓杰
机构地区 大庆油田总医院
出处 《中国伤残医学》 2012年第12期30-32,共3页 Chinese Journal of Trauma and Disability Medicine
关键词 CD20 原核表达 融合蛋白 抗体制备 淋巴瘤 CD20 Prokaryotic expression Fusion protein Antibody
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参考文献10

  • 1Junji Uchidal,Youngkyun Lee,Minoru Hasegawa,et al.MouseCD20expression and function[J].International Immunology,2004,16(1):119-129.
  • 2Arzoo K,Sadeghi S,Liebman HA.Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20monoclonal antibody(rituximab).Ann Rheum Dis online,2002,61:922-924.
  • 3C. M.Jubala, J. W. Wojcieszyn, V. E. O. Valli, D. M. Getzy ,et al, CD20 expression in normal canine B cells and in canine non-hodgkin lymphoma[J].Vet Pathol , 2005,42(4): 468-476.
  • 4李爱玲,孙瑛勋,洪海燕,于鸣,赵法伋,郭俊生,沈倍奋.利用基因重组抗原研制人CD20单克隆抗体及其功能的研究[J].中华微生物学和免疫学杂志,2002,22(4):385-388. 被引量:12
  • 5George Z.Rassidakis, L.Jeffrey Medeiros, Simonetta Viviani,et al. CD20 expression in hodgkin and reed-steinberg cells of classical hodgkin's disease : associations with presenting features and clinical outcome[J].JCO, 2002,20(5): 1278-1287.
  • 6Cheson BD.Radioimmunotherapy of non-Hodgkin lymphomas[J].Blood,2003,101(2):391-39.
  • 7Jessica L.Teeling,Ruth R.French,Mark S.Cragg,et al.Characterization of new human CD20monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas[J].Blood,2004,104(6):1793-1800.
  • 8刘荣,姜文国,刘芳,张砚君,范冬梅,杨铭,熊冬生,杨纯正.人4-1BBL胞外区/抗CD20融合蛋白的构建和表达[J].细胞与分子免疫学杂志,2008,24(6):543-545. 被引量:6
  • 9王玉刚,沈倍奋.CD20抗原及治疗性抗CD20抗体[J].中国肿瘤生物治疗杂志,2005,12(1):76-79. 被引量:10
  • 10Harjunp&a&a A,Junnikkala S,Meri S.Ritux imab(ant-iCD20)therapy of B-cell lymphomas:direct complementkilling is superior to cellular effector mechanisms.Scand JImmunol,2000;51:634-641.

二级参考文献28

  • 1姜文国,熊冬生,邵晓枫,王金宏,许元富,刘芳,郭红星,朱祯平,杨纯正.人4-1BBL胞外区基因的克隆与表达研究[J].生物工程学报,2005,21(5):703-707. 被引量:7
  • 2洪海燕 孙瑛勋 等.人CD20基因在鼠NIH-3T3细胞膜上的表达[J].Acta Biochinica et Biophysica Sinica(生物化学与生物物理学报:英文版),2000,32(4):430-433.
  • 3Tedder TF, McIntyre G, Schlossman SF. Heterogeneity in the B1 (CD20) cell surface molecule expressed by human B-lymphocytes[J]. Mol Immunol, 1988, 25(12): 1321-1330.
  • 4Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: Signaling through lipid rafts[J]. Immunology, 2002, 107(2): 176-182.
  • 5Shan D, Ledbetter JA, Press OW. Signaling events involved in anti-CD20-induced apoptosis of malignant human B cells[J]. Cancer Immunol Immunother, 2000, 48(12): 673-683.
  • 6Polyak MJ, Deans JP. Alanine-170 and proline-172 are critical determinants for extracellular CD20 epitopes; heterogeneity in the fine specificity of CD20 monoclonal antibodies is defined by additional requirements imposed by both amino acid sequence and quaternary structure[J]. Blood, 2002, 99(9): 3256-3262.
  • 7Ghetie MA, Bright H, Vitetta ES. Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin[J]. Blood, 2001, 97(5): 1392-1398.
  • 8Krasner C, Joyce RM. Zevalin: 90yttrium labeled anti-CD20 (ibritumomab tiuxetan), a new treatment for non-Hodgkin's lymphoma[J]. Curr Pharm Biotechnol, 2001, 2(4): 341-349.
  • 9Bischof Delaloye A. The role of nuclear medicine in the treatment of non-Hodgkin's lymphoma (NHL)[J]. Leuk Lymphoma, 2003, 44 Suppl 4: S29-36.
  • 10Cheson BD. Radioimmunotherapy of non-Hodgkin lymphomas[J]. Blood, 2003, 101(2): 391-397.

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