重组抗体药物研究进展及应用

中国生物工程杂志

2009, Vol. 29

Issue (08): 102-106

综述

重组抗体药物研究进展及应用

张莹¹,何金生²,洪涛³

1. 北京交通大学理学院生命科学与生物工程研究院北京 1000442
2. 中国疾病预防控制中心病毒病预防控制所北京100052

Advances and Applications of Recombinant Antibody Drugs

ZHANG Ying¹, HE Jin-Sheng¹, HONG Chao^1,2

1.College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing100044,China
2.Institute for Viral Disease Control and Prevention, China CDC, Beijing100052,China

全文: PDF(455 KB) HTML

摘要：

重组抗体药物的发展经历了鼠源单克隆抗体（McAb）、人鼠嵌合抗体、人源化抗体和全人抗体等阶段，目前初步应用于抗肿瘤、抗自身免疫病、抗感染等领域。保持和提高抗体的亲和力、降低抗体的免疫原性是抗体药物基因工程改造的两大原则。在嵌合抗体成功的基础上，通过CDR移植、表面修饰、抗体库以及转基因鼠技术，逐步提高人源化程度至100%。然而，实验室水平的研究结果与实际应用仍然存在一定差距。就重组抗体药物的基本概况、现存的问题与可能的解决办法以及在肿瘤、病毒性疾病和阿尔茨海默病治疗上的应用情况等进行了综述。

关键词： 重组抗体药物;单克隆抗体;抗体人源化

Abstract:

Recombinant antibody drugs has developed through mice monoclonal antibody（McAb）, humanmice chimeric antibody, humanized antibody and full human antibody. They have been applied in clinical immunotherapy for the treatment of cancer, autoimmune diseases, viral diseases and Alzheimer disease, etc. The two basic principles in antibody humanization are keeping or enhancing affinity and reducing immunogenicity of engineered antibodies. The degree of humanization has approached 100% following the continuously improved techniques, such as CDR grafting, resurfacing, antibody library and transgenic mice. However, the gap between the basic research and clinical application still need to be filled. The outline, challenge and perspective in application associated to recombinant antibody drugs were reviewed here.

Key words: Recombinant antibody drugs Monoclonal antibody humanization

收稿日期: 2009-04-15 出版日期: 2009-07-28

ZTFLH:

Q819

基金资助:

国家“863”计划（2006AA02A247）资助项目

通讯作者: 张莹

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引用本文:

张莹,何金生,洪涛. 重组抗体药物研究进展及应用[J]. 中国生物工程杂志, 2009, 29(08): 102-106.

ZHANG Ying, HE Jin-Sheng, HONG Chao. Advances and Applications of Recombinant Antibody Drugs. China Biotechnology, 2009, 29(08): 102-106.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I08/102

［1］ Morrison S L, Johnson M J, Herzenberg L A, et al. Chimeric human antibody molecules: Mouse antigenbinding domains with human constant region domains. Proc Natl Acad Sci USA, 1984, 81: 6851~6855
［2］沈倍奋，陈志南，刘民培. 重组抗体. 北京：科学出版社，2005.217~234
Shen B F, Chen Z N, Liu M P. Beijing: Science Press,2005.217~234
［3］沈倍奋. 抗体药物研究进展. 第二军医大学学报, 2002, 23 (10): 1047~1049
Shen B F. Acad J Sec Mil Med Univ, 2002, 23 (10): 1047~1049
［4］ Booy E P, Johar D, Maddika S,et al. Monoclonal and bispecific antibodies as novel therapeutics.
［5］陈志南. 基于抗体的中国生物制药产业化前景. 中国医药生物技术, 2007, 2 (1): 2~5
Chen Z N. Chin Med Biotechol, 2007, 2 (1): 2~5
［6］ Hwang W Y, Foote J. Immunogenicity of engineered antibodies. Methods, 2005, 36 (1):3~10
［7］ Kashmiri S V, De Pascalis R, Gonzales N R, et al. SDR grafting——a new approach to antibody humanization. Methods, 2005, 36 (1):25~34
［8］ Clark M. Antibody humanization: a case of the ‘Emperor’s new clothes’? Immunol Today, 2000, 21 (8):397~402
［9］ Leonard J P, Coleman M, Ketas J C, et al. Epratuzumab, a humanized antiCD22 antibody, in aggressive nonHodgkin’s lymphoma. Clin Cancer Res, 2004, 10 (16): 5327~5334
［10］中国首个基因重组人源化单克隆抗体药物上市. 中国医药生物技术. 2008, 3 (5): 384
Chin Med Biotechol, 2008, 3 (5): 384
［11］ Haymes L M, Tonkin J, Anderson L J, et al. Neutralizing antiF glycoprotein and antisubstance Pantibody treatment effectively reduces infection and inflammation associated with respiratory syncytial virus infection. J Virol, 2002, 76 (14): 6873~6881
［12］ Lambert M P, Barlow A K, Chromy B A, et al. Diffusible, nonfibrillar ligands derived from Abeta142 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A, 1998, 95 (11):6448~6453
［13］ Bard F, Cannon C, Barbour R, et al.Peripherally administered antibodies against amyloid betapeptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med, 2000, 6 (8):916~919
［14］ Lee E B, Leng L Z, Zhang B, et al. Targeting amyloidbeta peptide (Aβ) oligomers by passive immunization with a conformationselective monoclonal antibody improves learning and memory in Aβ precursor protein (APP) transgenic mice. J Biol Chem, 2006, 281 (7):4292~4299
［15］ Hawkes C A, McLaurin J. Clinical immunotherapy trials in Alzheimer’s disease. Drug Discovery Today: Therapeutic Strategies, 2008(in press)
［16］ Wilcock D M, Colton C A. Antiamyloidbeta immunotherapy in Alzheimer's disease: relevance of transgenic mouse studies to clinical trials. J Alzheimers Dis, 2008, 15 (4):555~569
［17］ Thakker D R, Weatherspoon M R, Harrison J, et al. Intracerebroventricular amyloid{beta} antibodies reduce cerebral amyloid angiopathy and associated microhemorrhages in aged Tg2576 mice. Proc Natl Acad Sci U S A, 2009, 25(in press)
［18］ Weinblatt M E, Keystone E C, Furst D E, et al. Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study. Ann Rheumatic Dis, 2006, 65 (6): 753~759

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