Monoclonal antibody targeting of cell surface CD20 on B-cell malignancies by rituximab (Rituxan) has been a promising therapy for several hematological malignancies. However, many of these patients relapse after treatment. Herbst et al. investigated the ability to target B-cell surface CD19 and improve the antibody-directed cellular cytotoxicity (ADCC) by using an afucosylated form of the monoclonal antibody (mAb). MEDI-551 is a new afucosylated anti-CD19 mAb optimized for enhanced ADCC. MEDI-551 depletes B cells at lower mAb doses than rituximab and was more effective at depleting blood and tissue B cells in a double transgenic mouse model. Unlike rituximab, MEDI-551 does not rely on complement-dependent cytotoxicity for part of its efficacy. MEDI-551 also resulted in extended B-cell depletion from blood and spleen relative to rituximab treatment, probably due to bone marrow B-cell depletion. MEDI-551 represents a new anti-CD19 mAb with enhanced ADCC function that has potential as a new form of treatment for B-cell malignancies and potentially B-cell-dependent autoimmune diseases.
See article at J Pharmacol Exp Ther 2010, 335:213–222.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics