Ame-133v, A Humanized, Fc-Engineered Anti-Cd20 Monoclonal Antibody, Demonstrates Greater B Cell Depletion Than Rituxan In Vitro

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Purpose The efficacy of AME-133v in depleting B lymphocytes was compared in vitro to that of Rituxan, and the effect of FcαRIII genotype was assessed. Methods Blood samples from 37 healthy donors were collected and genotyped for FcαRIII polymorphism. Varying concentrations of AME-133v or Rituxan were applied to samples and CD19+ peripheral circulating B lymphocytes were measured using fluorescence-activated cell sorting (FACS). B cell depletion was listed as a percentage of baseline level. Results In an in vitro whole blood assay, AME-133v was more effective in depleting B lymphocytes from baseline levels than Rituxan, particularly at increasing concentrations (Table 1). Significant differences were found between treatments averaged over doses, between doses averaged over treatments, and between treatments depending on dose, all with p<0.0001. AME-133v's superior effect in depleting B cells is independent of dose (p<0.001), but caused greater B cell depletion at lower concentrations of antibody. In both AME-133v and Rituxan treatments, VF and FF patients demonstrated less B cell depletion, corroborating previous data citing decreased response to Rituxan among F-carriers and indicating improved pharmacodynamics of AME-133v. Conclusion AME-133v is engineered for a 6-fold more potent effector function in antibody-dependent cell-mediated cytotoxicity (ADCC) compared to Rituxan, which is elucidated through improved B cell depletion, across doses. Depletion in AME-133v-treated patients was also greater across all genotypes, suggesting superior pharmacodynamics of AME-133v in the low-responding F-carrier population. These findings indicate relevant biological activity of the antibody and suggest that AME-133v may provide additional clinical benefit for low-affinity FcαRIII patients. A randomized trial is being planned to compare clinical efficacy of AME-133v vs. Rituxan, targeting low-affinity FcαRIII patients. ![Figure][1] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3784. doi:1538-7445.AM2012-3784 [1]: pending:yes