Antibody Fragments: Hope and Hype

Overview

Journal MAbs

Specialty Allergy & Immunology

Date 2010 Jan 23

PMID 20093855

Citations 133

Authors

Aaron L Nelson

Affiliations

Soon will be listed here.

Abstract

The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and "third generation" (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.

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References

Holt L, Basran A, Jones K, Chorlton J, Jespers L, Brewis N . Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. Protein Eng Des Sel. 2008; 21(5):283-8. DOI: 10.1093/protein/gzm067. View

Yokota T, Milenic D, Whitlow M, Schlom J . Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992; 52(12):3402-8. View

Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, Hanakam F . Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer. 2002; 100(6):690-7. DOI: 10.1002/ijc.10557. View

Hu S, Shively L, Raubitschek A, Sherman M, Williams L, Wong J . Minibody: A novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer Res. 1996; 56(13):3055-61. View

Jain R . Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. Cancer Res. 1990; 50(3 Suppl):814s-819s. View

Cumber A, Ward E, Winter G, Parnell G, Wawrzynczak E . Comparative stabilities in vitro and in vivo of a recombinant mouse antibody FvCys fragment and a bisFvCys conjugate. J Immunol. 1992; 149(1):120-6. View

Hayden M, Linsley P, Gayle M, Bajorath J, Brady W, Norris N . Single-chain mono- and bispecific antibody derivatives with novel biological properties and antitumour activity from a COS cell transient expression system. Ther Immunol. 1994; 1(1):3-15. View

Pappas D, Bathon J, Hanicq D, Yasothan U, Kirkpatrick P . Golimumab. Nat Rev Drug Discov. 2009; 8(9):695-6. DOI: 10.1038/nrd2982. View

Nelson A, Reichert J . Development trends for therapeutic antibody fragments. Nat Biotechnol. 2009; 27(4):331-7. DOI: 10.1038/nbt0409-331. View

10.

Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle P . Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol. 2005; 43(6):763-71. DOI: 10.1016/j.molimm.2005.03.007. View

11.

Chames P, Baty D . Bispecific antibodies for cancer therapy: the light at the end of the tunnel?. MAbs. 2010; 1(6):539-47. PMC: 2791310. DOI: 10.4161/mabs.1.6.10015. View

12.

Kurucz I, Titus J, Jost C, Segal D . Correct disulfide pairing and efficient refolding of detergent-solubilized single-chain Fv proteins from bacterial inclusion bodies. Mol Immunol. 1995; 32(17-18):1443-52. DOI: 10.1016/0161-5890(95)00105-0. View

13.

Holt L, Herring C, Jespers L, Woolven B, Tomlinson I . Domain antibodies: proteins for therapy. Trends Biotechnol. 2003; 21(11):484-90. DOI: 10.1016/j.tibtech.2003.08.007. View

14.

Jain A, Jain S . PEGylation: an approach for drug delivery. A review. Crit Rev Ther Drug Carrier Syst. 2008; 25(5):403-47. DOI: 10.1615/critrevtherdrugcarriersyst.v25.i5.10. View

15.

Zeidler R, Reisbach G, Wollenberg B, Lang S, Chaubal S, Schmitt B . Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing. J Immunol. 1999; 163(3):1246-52. View

16.

Bird R, HARDMAN K, Jacobson J, Johnson S, Kaufman B, Lee S . Single-chain antigen-binding proteins. Science. 1988; 242(4877):423-6. DOI: 10.1126/science.3140379. View

17.

Reichert J, Valge-Archer V . Development trends for monoclonal antibody cancer therapeutics. Nat Rev Drug Discov. 2007; 6(5):349-56. DOI: 10.1038/nrd2241. View

18.

Sanz L, Cuesta A, Compte M, Alvarez-Vallina L . Antibody engineering: facing new challenges in cancer therapy. Acta Pharmacol Sin. 2005; 26(6):641-8. DOI: 10.1111/j.1745-7254.2005.00135.x. View

19.

Milstein C, Cuello A . Hybrid hybridomas and their use in immunohistochemistry. Nature. 1983; 305(5934):537-40. DOI: 10.1038/305537a0. View

20.

Reichert J . Monoclonal antibodies as innovative therapeutics. Curr Pharm Biotechnol. 2008; 9(6):423-30. DOI: 10.2174/138920108786786358. View