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The biology of CD20 and its potential as a target for mAb therapy

The biology of CD20 and its potential as a target for mAb therapy
The biology of CD20 and its potential as a target for mAb therapy
CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus. Despite the success in immunotherapy, knowledge about the biology of CD20 is still relatively scarce, partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype. However, interesting insight has come from work showing that CD20 is resident in lipid raft domains of the plasma membrane where it probably functions as a store-operated calcium channel following ligation of the B cell receptor for antigen. In the current review, these and data relating to its activity as a therapeutic target will be discussed in depth. It is clear that a greater understanding of CD20 biology and the effector mechanisms, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and growth regulation, which operate with anti-CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic target.
140-174
Karger
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Walshe, C.A.
6ddd7e8d-cce3-4e02-993c-7ca43a3e9871
Ivanov, A.O.
308c6f3c-3627-4a60-bc2b-68c2d9d56ca1
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Stohl, W.
Cragg, M.S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Walshe, C.A.
6ddd7e8d-cce3-4e02-993c-7ca43a3e9871
Ivanov, A.O.
308c6f3c-3627-4a60-bc2b-68c2d9d56ca1
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Stohl, W.

Cragg, M.S., Walshe, C.A., Ivanov, A.O. and Glennie, M.J. (2005) The biology of CD20 and its potential as a target for mAb therapy. In, Stohl, W. (ed.) B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease. (Current Directions in Autoimmunity, , (doi:10.1159/000082102), 8) Karger, pp. 140-174. (doi:10.1159/000082102).

Record type: Book Section

Abstract

CD20 is a 33-37 kDa, non-glycosylated phosphoprotein expressed on the surface of almost all normal and malignant B cells. It is also the target for rituximab, the most effective anti-cancer monoclonal antibody developed to date. Rituximab has now been given to over 300,000 lymphoma patients in the last decade and interestingly is now being explored for use in other disorders, such as autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus. Despite the success in immunotherapy, knowledge about the biology of CD20 is still relatively scarce, partly because it has no known natural ligand and CD20 knockout mice display an almost normal phenotype. However, interesting insight has come from work showing that CD20 is resident in lipid raft domains of the plasma membrane where it probably functions as a store-operated calcium channel following ligation of the B cell receptor for antigen. In the current review, these and data relating to its activity as a therapeutic target will be discussed in depth. It is clear that a greater understanding of CD20 biology and the effector mechanisms, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and growth regulation, which operate with anti-CD20 mAb in vivo will allow more efficient exploitation of CD20 as a therapeutic target.

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Published date: 2005

Identifiers

Local EPrints ID: 26263
URI: https://eprints.soton.ac.uk/id/eprint/26263
PURE UUID: 1ed931ab-9fa7-4b53-bbcf-b8a7f3e4d3c9
ORCID for M.S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 19 Apr 2006
Last modified: 16 Jul 2019 01:04

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