David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments

被引:147
作者
Bates, Adam [1 ]
Power, Christine A. [1 ]
机构
[1] GlaxoSmithKline, Biopharm Mol Discovery, Stevenage SG1 2NY, Herts, England
来源
ANTIBODIES | 2019年 / 8卷 / 02期
关键词
ADC; antibody fragments; BiTE (R); diabodies; domain antibodies; fab; ImmTAC((R)); Nanobody((R)); scFv; TandAb; V-NAR; SINGLE-CHAIN FV; BLOOD-BRAIN-BARRIER; IN-VIVO; DOMAIN ANTIBODIES; FAB FRAGMENT; PROTEIN-L; VARIABLE DOMAINS; PICHIA-PASTORIS; NEXT-GENERATION; ANTIGEN-BINDING;
D O I
10.3390/antib8020028
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications. The development of smaller, antigen binding antibody fragments, derived from conventional antibodies or produced recombinantly, has been growing at a fast pace. Antibody fragments can be used on their own or linked to other molecules to generate numerous possibilities for bispecific, multi-specific, multimeric, or multifunctional molecules, and to achieve a variety of biological effects. They offer several advantages over full-length monoclonal antibodies, particularly a lower cost of goods, and because of their small size they can penetrate tissues, access challenging epitopes, and have potentially reduced immunogenicity. In this review, we will discuss the structure, production, and mechanism of action of EMA/FDA-approved fragments and of those in clinical and pre-clinical development. We will also discuss current topics of interest surrounding the potential use of antibody fragments for intracellular targeting and blood-brain barrier (BBB) penetration.
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页数:31
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