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Building better magic bullets — improving unconjugated monoclonal antibody therapy for cancer

Nature Reviews Cancer volume 7, pages 701–706 (2007)Cite this article

Abstract

The potential of monoclonal antibodies to effectively treat cancer is beginning to be widely acknowledged. Advances in antibody engineering make it possible to produce various recombinant proteins that exploit the specificity of the antibody-combining site to manipulate tumour-related signalling, and to stimulate anti-tumour immune responses. Future advances in the field will rely on the improved identification of functional antibody targets to perturb cancer-relevant signalling, and by the improved selection of tumours that can be effectively treated. These advances will be complemented by the use of antibodies that induce clinically meaningful host-protective immune responses. But, can we afford this progress?

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Figure 1: The structure of a human IgG antibody.

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Authors and Affiliations

  1. Louis M. Weiner is at the Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19,111, USA. Louis.Weiner@fccc.edu,

    Louis M. Weiner

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Glossary

Antibody valence

The number of different molecules an antibody can combine with at one time.

B-cell idiotype

A unique immunoglobulin sequence variant, typically in the antibody complementarity-determining regions (CDRs).

Bispecific antibodies

Antibodies with two distinct binding specificities (such as ERBB2 and CD16), which can be prepared by fusing two distinct hybridomas, through chemical conjugation, or using recombinant antibody engineering techniques.

Complement

A heat-labile component of normal plasma that contains many proteins acting together to augment opsonization of targets by antibodies and promote antibody-mediated target destruction by forming membrane-attack complexes that form pores in target cell membranes, and also leads to clearance of immune complexes.

Diabodies

Recombinant antibodies composed of two single-chain Fv molecules joined by a very short amino acid linker that 'forces' the protein into a divalent binding format that confers intermediate properties compared with the scFv and minibody formats.

Minibodies

Recombinant antibodies composed of scFvs fused to antibody Fc domain elements to create a divalent molecule with pharmacological properties that more closely resemble those of intact IgG immunoglobulins.

Single-chain Fv fragments

(scFv) Small (25 kDa) proteins that consist of variable-heavy and variable-light chain genes joined by a short amino acid linker that recapitulate an intact antibody binding site, but exhibit rapid tumour penetration and systemic clearance.

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Weiner, L. Building better magic bullets — improving unconjugated monoclonal antibody therapy for cancer. Nat Rev Cancer 7, 701–706 (2007). https://doi.org/10.1038/nrc2209

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