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Thursday 06 July 2006

Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower concentrations and more effectively than rituximab.

By: Bowles JA, Wang SY, Link BK, Allen B, Beuerlein G, Campbell MA, Marquis D, Ondek B, Wooldridge JE, Smith BJ, Breitmeyer JB, Weiner GJ.

Blood 2006 Jul 6; [Epub ahead of print]

Growing evidence indicates the affinity of mAb for CD16 (FcgammaRIII) plays a central role in the ability of the mAb to mediate anti-tumor activity. We evaluated how CD16 polymorphisms, and mAb with modified affinity for target antigen and CD16, impact on NK cell phenotype when CD20 (+) lymphoma cells were also present. MAb consisted of rituximab (R), anti-CD20 with enhanced affinity for CD20 (AME-B), and anti-CD20 with enhanced affinity for both CD20 and CD16 (AME-D). Higher concentrations of mAb were needed to induce CD16 modulation, CD54 upregulation, and ADCC on NK cells from subjects with the lower affinity CD16 polymorphism. The dose of mAb needed to induce NK activation was lower with AME-D irrespective of CD16 polymorphism. At saturating mAb concentrations, peak NK activation was greater for AME-D. Similar results were found with measurement of CD16 modulation, CD54 upregulation and ADCC. These data demonstrate tumor cells coated with mAb with enhanced affinity for CD16 are more effective at activating NK cells at both low and saturating mAb concentrations irrespective of CD16 polymorphism, and provide further evidence for the clinical development of such mAb with the goal of improving clinical response to mAb.

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