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

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Blood First Edition Paper, prepublished online June 26, 2008; DOI

10.1182/blood-2008-04-149161.

Type II (tositumomab) anti-CD20 monoclonal antibody out performs Type I

(rituximab-like) reagents in B-cell depletion regardless of complement

activation

A Beers, Claude HT Chan, Sonya , Ruth R French, Kathrine E

Attfield, M Brennan, Anupama Ahuja, Mark J Shlomchik, Mark S Cragg, and

J Glennie*

Tenovus Laboratory, Cancer Sciences Division, Southampton University School of

Medicine, General Hospital, Southampton, Hampshire, United Kingdom

Department of Laboratory Medicine, Yale University School of Medicine, New

Haven, CT, United States

* Corresponding author; email: mjg@... .

Anti-CD20 mAb 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 mAb directly in vivo and maximize Fc effector function, we selected and

engineered mAb 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, opsonising 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, since Type I

mAb 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 mAb in human B cell diseases.