The University of Southampton
University of Southampton Institutional Repository

Antibody modulation: Limiting the efficacy of therapeutic antibodies

Antibody modulation: Limiting the efficacy of therapeutic antibodies
Antibody modulation: Limiting the efficacy of therapeutic antibodies
Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease. From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and unique mechanisms of action. These two facets have allowed them to (a) be integrated rapidly into clinical practice in combination with conventional radio- and chemo-therapies and (b) to avoid the resistance mechanisms typically observed with classical small molecule drugs, such as upregulation of drug efflux transporters, dysregulation of apoptosis and mutations in key target enzymes/pathways.

Although success with mAb therapies has been impressive, they are also subject to their own resistance mechanisms. In this perspective we discuss the various ways in which mAb therapeutics can be inhibited, concentrating mainly on the ways in which they can be removed from the target cell surface—a process called modulation. This can be achieved either in a cis-fashion on a single cell or in trans, precipitated by engagement with a second phagocytic cell. The evidence for each of these processes will be discussed, in addition to possible therapeutic strategies that might be employed to inhibit or reverse them.
antibodies, Fc gamma receptor, Fc?RIIB, modulation, shaving, immunotherapy, CD20, tumour resistance
1043-6618
269-275
Vaughan, Andrew T.
bfb2ceab-a592-457e-89f9-00fcd1dddbdb
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Vaughan, Andrew T.
bfb2ceab-a592-457e-89f9-00fcd1dddbdb
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2

Vaughan, Andrew T., Cragg, Mark and Beers, Stephen A. (2015) Antibody modulation: Limiting the efficacy of therapeutic antibodies. Pharmacological Research, 99, 269-275. (doi:10.1016/j.phrs.2015.07.003). (PMID:26188150)

Record type: Article

Abstract

Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease. From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and unique mechanisms of action. These two facets have allowed them to (a) be integrated rapidly into clinical practice in combination with conventional radio- and chemo-therapies and (b) to avoid the resistance mechanisms typically observed with classical small molecule drugs, such as upregulation of drug efflux transporters, dysregulation of apoptosis and mutations in key target enzymes/pathways.

Although success with mAb therapies has been impressive, they are also subject to their own resistance mechanisms. In this perspective we discuss the various ways in which mAb therapeutics can be inhibited, concentrating mainly on the ways in which they can be removed from the target cell surface—a process called modulation. This can be achieved either in a cis-fashion on a single cell or in trans, precipitated by engagement with a second phagocytic cell. The evidence for each of these processes will be discussed, in addition to possible therapeutic strategies that might be employed to inhibit or reverse them.

PDF
Vaughana_Antibody.pdf - Accepted Manuscript
Download (578kB)

More information

Accepted/In Press date: 9 July 2015
e-pub ahead of print date: 15 July 2015
Published date: September 2015
Keywords: antibodies, Fc gamma receptor, Fc?RIIB, modulation, shaving, immunotherapy, CD20, tumour resistance
Organisations: Cancer Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 382724
URI: https://eprints.soton.ac.uk/id/eprint/382724
ISSN: 1043-6618
PURE UUID: 79e905b5-e38b-4f0f-bb4f-9f16ae5e0ef7
ORCID for Andrew T. Vaughan: ORCID iD orcid.org/0000-0001-6076-3649
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 27 Oct 2015 15:39
Last modified: 06 Jun 2018 12:58

Export record

Altmetrics

Contributors

Author: Andrew T. Vaughan ORCID iD
Author: Mark Cragg ORCID iD

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×