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Cited by 237Monoclonal and Polyclonal Antibodies ResearchProtein purification and stabilityBiosimilars and Bioanalytical Methods

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

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Bates, Adam, Power, Christine A.·2019·Antibodies
DOI 10.3390/antib8020028PMC PMC6640713
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Abstract

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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  • Fab and scFv are the most used and widespread antibody-like formats.

    “Despite that several alternative antibody-like formats derived from different Ig-like domain combinations are continuously developed and proposed [1] such as single-domain antibody fragments (dAbs), the antigen-binding fragments (Fab) and single-chain variable fragments (scFv) are those most used and widespread.”

    From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [1]

    Section 2.2 reports that Fabs account for approximately 49% of antibody fragments entering clinical trials, supporting their prominence. Section 2.1 gives examples of scFvs in clinical development, but the paper does not establish that Fab and scFv are together the most used and widespread formats across all applications. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The three main antibody surrogates, single-domain antibodies, scFv and Fabs, are continuously developed and reformatted into bispecific/multi-specific molecules or cytotoxic/radioactive drug carriers for clinical applications.

    “Thanks to their improved pharmacokinetics and their structural and functional flexibility, the three main antibody surrogates, single-domain antibodies (dAbs), scFv and Fabs, are continuously developed and reformatted into bispecific/multi-specific molecules or cytotoxic/radioactive drug carriers to achieve a desired biological efficacy and for multiple clinical applications [1].”

    From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [1]

    The Introduction (section 1) identifies Fab, scFv and single-domain antibodies as modular fragments that can be linked into bispecific or multispecific molecules. The Oncology section (4.1.6) reports toxin and radioisotope conjugates with clinical applications. But the citing sentence’s blanket claim of improved pharmacokinetics is not supported: the Introduction says these fragments’ smaller size also causes faster renal excretion, potentially requiring higher or more frequent doses. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Antibody fragments are widely utilized in therapeutic and diagnostic applications as well as basic life science research.

    “Antibody fragments are widely utilized in therapeutic and diagnostic applications as well as in basic life science research [1].”

    From Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments (2020) · cites this paper as [1]

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Authors
Bates, A., & Power, C. A.
Affiliations
  • GlaxoSmithKline (United Kingdom) (GB)
  • Biopharm Molecular Discovery, GlaxoSmithKline, Hertfordshire SG1 2NY, UK
ORCID
Bates, Adam
Venue
Antibodies
Publisher
MDPI AG
Published
2019-04-09
Volume
8
Issue
2
Pages
28
ISSN
2073-4468 (ISSN-L)
DOI
10.3390/antib8020028
PMC
PMC6640713
OpenAlex
W2937873741
Cited by
237
References
149
Citations by year
2026: 26 · 2025: 40 · 2024: 25 · 2023: 46 · 2022: 35 · 2021: 38 · 2020: 18 · 2019: 9
FWCI
3.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Antibodies (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Amgen
  • Eli Lilly and Company
  • AstraZeneca
  • GlaxoSmithKline
  • Novartis
  • Biogen
  • Ablynx
  • MacroGenics
  • Genentech
  • UCB Pharma
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
Keywords
antibody fragments, monoclonal antibodies, bispecific antibodies, multispecific antibodies, antibody engineering, subcellular targeting, blood-brain barrier penetration, immunogenicity, antibody structure, antibody production, mechanism of action, biopharmaceuticals

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