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Mechanisms of killing by anti-CD20 monoclonal antibodies

Mechanisms of killing by anti-CD20 monoclonal antibodies
Mechanisms of killing by anti-CD20 monoclonal antibodies
CD20 is a cell-surface marker expressed on mature B cells and most malignant B cells, but not stem or plasma cells. It is an ideal target for monoclonal antibodies (mAb), such as rituximab and ofatumumab, as it is expressed at high levels on most B-cell malignancies, but does not become internalized or shed from the plasma membrane following mAb treatment. This allows mAb to persist on the cell surface for extended periods and deliver sustained immunological attack from complement and FcR-expressing innate effectors, particularly macrophages. CD20 can also generate transmembrane signals when engaged by certain mAb which, although unproven, might provide an important element of the therapeutic success of anti-CD20 mAb. These favourable characteristics have led to anti-CD20 mAb being developed and exploited for use in immunotherapy, where they have proven remarkably efficacious in both the treatment of malignant disease and autoimmune disorders by deleting malignant or normal B cells, respectively. In this review, we discuss how these mAb have driven research in the immunotherapy field over the last decade, detail their likely modes of action and their limitations in terms of effector exhaustion, and explore ways in which they might be enhanced and further exploited in the future.
chronic lymphocytic-leukemia, the shaving reaction, cells, pcd, innate, therapeutic activity, cdc, non-hodgkins-lymphoma, disease, lived plasma-cells, cell, fc-gamma receptors, monoclonal antibody, monoclonal-antibodies, immunotherapy, b cell, adcc, cd20, complement-mediated lysis, rituximab, systemic-lupus-erythematosus, mechanism, human b-cells, rituximab in-vitro, effector exhaustion, dependent cellular cytotoxicity
0161-5890
3823-3837
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Taylor, Ronald P.
02ce2f21-dd77-491d-88e9-b495990cb5a0
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Taylor, Ronald P.
02ce2f21-dd77-491d-88e9-b495990cb5a0

Glennie, Martin J., French, Ruth R., Cragg, Mark S. and Taylor, Ronald P. (2007) Mechanisms of killing by anti-CD20 monoclonal antibodies. Molecular Immunology, 44 (16), 3823-3837. (doi:10.1016/j.molimm.2007.06.151).

Record type: Article

Abstract

CD20 is a cell-surface marker expressed on mature B cells and most malignant B cells, but not stem or plasma cells. It is an ideal target for monoclonal antibodies (mAb), such as rituximab and ofatumumab, as it is expressed at high levels on most B-cell malignancies, but does not become internalized or shed from the plasma membrane following mAb treatment. This allows mAb to persist on the cell surface for extended periods and deliver sustained immunological attack from complement and FcR-expressing innate effectors, particularly macrophages. CD20 can also generate transmembrane signals when engaged by certain mAb which, although unproven, might provide an important element of the therapeutic success of anti-CD20 mAb. These favourable characteristics have led to anti-CD20 mAb being developed and exploited for use in immunotherapy, where they have proven remarkably efficacious in both the treatment of malignant disease and autoimmune disorders by deleting malignant or normal B cells, respectively. In this review, we discuss how these mAb have driven research in the immunotherapy field over the last decade, detail their likely modes of action and their limitations in terms of effector exhaustion, and explore ways in which they might be enhanced and further exploited in the future.

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More information

Published date: September 2007
Additional Information: XIth European meeting on Complement in Human Disease
Keywords: chronic lymphocytic-leukemia, the shaving reaction, cells, pcd, innate, therapeutic activity, cdc, non-hodgkins-lymphoma, disease, lived plasma-cells, cell, fc-gamma receptors, monoclonal antibody, monoclonal-antibodies, immunotherapy, b cell, adcc, cd20, complement-mediated lysis, rituximab, systemic-lupus-erythematosus, mechanism, human b-cells, rituximab in-vitro, effector exhaustion, dependent cellular cytotoxicity

Identifiers

Local EPrints ID: 62755
URI: http://eprints.soton.ac.uk/id/eprint/62755
ISSN: 0161-5890
PURE UUID: 65001838-be2a-4f1c-9dd0-c8d22599c6b2
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 02:58

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Contributors

Author: Ruth R. French
Author: Mark S. Cragg ORCID iD
Author: Ronald P. Taylor

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