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
相关论文
共 144 条
[21]   Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies [J].
De Genst, E ;
Silence, K ;
Decanniere, K ;
Conrath, K ;
Loris, R ;
Kinne, R ;
Muyldermans, S ;
Wyns, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (12) :4586-4591
[22]  
DECHATEAU M, 1993, SCAND J IMMUNOL, V37, P399
[23]   Repressible promoters - A novel tool to generate conditional mutants in Pichia pastoris [J].
Delic, Marizela ;
Mattanovich, Diethard ;
Gasser, Brigitte .
MICROBIAL CELL FACTORIES, 2013, 12
[24]   Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection [J].
Detalle, Laurent ;
Stohr, Thomas ;
Palomo, Concepcion ;
Piedra, Pedro A. ;
Gilbert, Brian E. ;
Mas, Vicente ;
Millar, Andrena ;
Power, Ultan F. ;
Stortelers, Catelijne ;
Allosery, Koen ;
Melero, Jose A. ;
Depla, Erik .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2016, 60 (01) :6-13
[25]   An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety [J].
Drake, Penelope M. ;
Rabuka, David .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2015, 28 :174-180
[26]   The therapeutic monoclonal antibody market [J].
Ecker, Dawn M. ;
Jones, Susan Dana ;
Levine, Howard L. .
MABS, 2015, 7 (01) :9-14
[27]   A novel platform for engineering blood-brain barrier-crossing bispecific biologics [J].
Farrington, Graham K. ;
Caram-Salas, Nadia ;
Haqqani, Arsalan S. ;
Brunette, Eric ;
Eldredge, John ;
Pepinsky, Blake ;
Antognetti, Giovanna ;
Baumann, Ewa ;
Ding, Wen ;
Garber, Ellen ;
Jiang, Susan ;
Delaney, Christie ;
Boileau, Eve ;
Sisk, William P. ;
Stanimirovic, Danica B. .
FASEB JOURNAL, 2014, 28 (11) :4764-4778
[28]  
Felices M., 2016, Blood, V128
[29]   Therapeutic application of antibody fragments in autoimmune diseases: current state and prospects [J].
Fernandes, Joao C. .
DRUG DISCOVERY TODAY, 2018, 23 (12) :1996-2002
[30]   Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory [J].
Ferndahl, Cecilia ;
Bonander, Nicklas ;
Logez, Christel ;
Wagner, Renaud ;
Gustafsson, Lena ;
Larsson, Christer ;
Hedfalk, Kristina ;
Darby, Richard A. J. ;
Bill, Roslyn M. .
MICROBIAL CELL FACTORIES, 2010, 9