Submitted April 4, 2008
Accepted June 3, 2008
Type II (tositumomab) anti-CD20 monoclonal antibody out performs Type I (rituximab-like) reagents in B-cell depletion regardless of complement activation
Stephen A Beers, Claude HT Chan, Sonya James, Ruth R French, Kathrine E Attfield, Claire M Brennan, Anupama Ahuja, Mark J Shlomchik, Mark S Cragg, and Martin 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{at}soton.ac.uk.
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.
