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Type II (tositumomab) anti-CD20 monoclonal antibody out performs type 1 (rituximab-like) reagents in B-cell depletion regardless of complement activation

Type II (tositumomab) anti-CD20 monoclonal antibody out performs type 1 (rituximab-like) reagents in B-cell depletion regardless of complement activation
Type II (tositumomab) anti-CD20 monoclonal antibody out performs type 1 (rituximab-like) reagents in B-cell depletion regardless of complement activation
Anti-CD20 monoclonal antibodies (mAbs) are classified into type I (rituximab-like) or type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare type I and II mAbs directly in vivo and maximize Fc effector function, we selected and engineered mAbs with the same mouse IgG2a isotype and assessed their B-cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonizing activity for phagocytosis, and in vivo half-life, the type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular, the spleen. Failure to engage complement did not explain the efficacy of the type II reagents because type I mAbs mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of type II CD20 mAbs in human B-cell diseases
0006-4971
4170-4177
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Chan, Claude H.T.
7b9dbc0f-c61e-4f9e-a3ac-83abb2034529
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Attfield, Katherine E.
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Brennan, Claire M.
e9406d16-eba7-45e8-8db3-54921949850c
Ahuja, Anupama
2c5d7a57-22b3-472b-939d-8073b05291ed
Shlomchik, Mark J.
fd126a66-c802-4204-bda8-ebb4dcdc5152
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Beers, Stephen A.
a02548be-3ffd-41ab-9db8-d6e8c3b499a2
Chan, Claude H.T.
7b9dbc0f-c61e-4f9e-a3ac-83abb2034529
James, Sonya
764c80e3-5bea-4b34-a871-b43f87ef97b0
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Attfield, Katherine E.
5a56874d-0f44-4890-813c-353865541fee
Brennan, Claire M.
e9406d16-eba7-45e8-8db3-54921949850c
Ahuja, Anupama
2c5d7a57-22b3-472b-939d-8073b05291ed
Shlomchik, Mark J.
fd126a66-c802-4204-bda8-ebb4dcdc5152
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded

Beers, Stephen A., Chan, Claude H.T., James, Sonya, French, Ruth R., Attfield, Katherine E., Brennan, Claire M., Ahuja, Anupama, Shlomchik, Mark J., Cragg, Mark S. and Glennie, Martin J. (2008) Type II (tositumomab) anti-CD20 monoclonal antibody out performs type 1 (rituximab-like) reagents in B-cell depletion regardless of complement activation. Blood, 112 (10), 4170-4177. (doi:10.1182/blood-2008-04-149161).

Record type: Article

Abstract

Anti-CD20 monoclonal antibodies (mAbs) are classified into type I (rituximab-like) or type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare type I and II mAbs directly in vivo and maximize Fc effector function, we selected and engineered mAbs with the same mouse IgG2a isotype and assessed their B-cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonizing activity for phagocytosis, and in vivo half-life, the type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular, the spleen. Failure to engage complement did not explain the efficacy of the type II reagents because type I mAbs mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of type II CD20 mAbs in human B-cell diseases

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Published date: November 2008
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 73216
URI: https://eprints.soton.ac.uk/id/eprint/73216
ISSN: 0006-4971
PURE UUID: 4b65ae30-a361-4aed-ab16-f35397dee919
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 03 Mar 2010
Last modified: 06 Jun 2018 12:58

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Contributors

Author: Claude H.T. Chan
Author: Sonya James
Author: Ruth R. French
Author: Katherine E. Attfield
Author: Claire M. Brennan
Author: Anupama Ahuja
Author: Mark J. Shlomchik
Author: Mark S. Cragg ORCID iD

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