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Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics

Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics
Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics
Since the turn of the century, cancer therapy has undergone a transformation in terms of new treatment modalities and renewed optimism in achieving long-lived tumour control and even cure. This is, in large part, thanks to the widespread incorporation of monoclonal antibodies (mAbs) into standard treatment regimens. These new therapies have, across many settings, significantly contributed to improved clinical responses, patient quality of life and survival. Moreover, the flexibility of the antibody platform has led to the development of a wide range of innovative and combinatorial therapies that continue to augment the clinician's armoury. Despite these successes, there is a growing awareness that in many cases mAb therapy remains suboptimal, primarily due to inherent limitations imposed by the immune system's own homeostatic controls and the immunosuppressive tumour microenvironment. Here, we discuss the principal barriers that act to constrain the tumour-killing activity of antibody-based therapeutics, particularly those involving antibody glycans, using illustrative examples from both pre-clinical and market approved mAbs. We also discuss strategies that have been, or are in development to overcome these obstacles. Finally, we outline how the growing understanding of the biological terrain in which mAbs function is shaping innovation and regulation in cancer therapeutics.
0959-6658
697-712
Dalziel, Martin
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Beers, Stephen
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Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Dalziel, Martin
966f5e8f-ac1b-4677-89ab-15f2a7dfcfbc
Beers, Stephen
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

Dalziel, Martin, Beers, Stephen, Cragg, Mark and Crispin, Max (2018) Through the barricades: overcoming the barriers to effective antibody-based cancer therapeutics. Glycobiology, 28 (9), 697-712. (doi:10.1093/glycob/cwy043).

Record type: Review

Abstract

Since the turn of the century, cancer therapy has undergone a transformation in terms of new treatment modalities and renewed optimism in achieving long-lived tumour control and even cure. This is, in large part, thanks to the widespread incorporation of monoclonal antibodies (mAbs) into standard treatment regimens. These new therapies have, across many settings, significantly contributed to improved clinical responses, patient quality of life and survival. Moreover, the flexibility of the antibody platform has led to the development of a wide range of innovative and combinatorial therapies that continue to augment the clinician's armoury. Despite these successes, there is a growing awareness that in many cases mAb therapy remains suboptimal, primarily due to inherent limitations imposed by the immune system's own homeostatic controls and the immunosuppressive tumour microenvironment. Here, we discuss the principal barriers that act to constrain the tumour-killing activity of antibody-based therapeutics, particularly those involving antibody glycans, using illustrative examples from both pre-clinical and market approved mAbs. We also discuss strategies that have been, or are in development to overcome these obstacles. Finally, we outline how the growing understanding of the biological terrain in which mAbs function is shaping innovation and regulation in cancer therapeutics.

Text
Dalziel et al. Glycobiology resubmission 10-April-18 - Accepted Manuscript
Restricted to Repository staff only until 12 June 2019.
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More information

Accepted/In Press date: 30 April 2018
e-pub ahead of print date: 12 June 2018

Identifiers

Local EPrints ID: 420271
URI: https://eprints.soton.ac.uk/id/eprint/420271
ISSN: 0959-6658
PURE UUID: 167c2d71-50d2-4dae-b23d-246becc95690
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 03 May 2018 16:30
Last modified: 14 Mar 2019 01:49

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