UNASSIGNED: Complement-dependent @entity137 (CDC) has been suggested to be an important mechanism of action of @entity5 -targeting Abs. However, single unmodified @entity470 ( @entity470 )-targeting IgG1 Abs fail to trigger efficient CDC. For the current study, we generated a CDC-optimized variant of the @entity470 Ab matuzumab (H425 wt) by introducing @entity3689 substitutions @entity68805 / @entity68806 (H425 mt). This Ab was then used to elucidate the impact of complement activation on the capacity of effector cells such as mononuclear cells (MNC) and polymorphonuclear cells (PMN) to exert @entity137 ( @entity137 ). H425 mt, but not H425 wt, significantly induced complement deposition, release of anaphylatoxins, and CDC against distinct @entity5 cell lines, whereas no differences in @entity137 by MNC or PMN were detected. Notably, stronger @entity137 was induced by H425 mt than by H425 wt in whole blood assays and in experiments in which MNC or PMN were combined with serum. Although MNC- @entity137 was not affected by C5 cleavage, the cytotoxic activity of PMN in the presence of serum strongly depended on C5 cleavage, pointing to a direct interaction between complement and PMN. Strong cell surface expression of @entity2242 receptors was detected on PMN, whereas NK cells completely lacked expression. Stimulation of PMN with @entity2242 led to upregulation of activated complement receptor 3, resulting in enhanced complement receptor 3-dependent PMN- @entity137 against @entity5 cells. In conclusion, complement-optimized @entity470 Abs may constitute a promising strategy to improve @entity5 cell killing by enhancing the interaction between humoral and cellular effector functions in Ab-based @entity5 therapy.

A Complement-Optimized XXXX Antibody Improves Cytotoxic Functions of Polymorphonuclear Cells against @entity5 Cells.

@entity68805 :: ('p|SUB|K|326|A', 'ProteinMutation') :: ['K326A'] @entity137 :: ('MESH:D064420', 'Disease') :: ['ADCC', 'Ab-dependent cell-mediated cytotoxicity', 'cytotoxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity68806 :: ('p|SUB|E|333|A', 'ProteinMutation') :: ['E333A'] @entity2242 :: ('728', 'Gene') :: ['C5a'] @entity3689 :: ('D000596', 'Chemical') :: ['amino acid']
@entity470 :: (1956,Gene) :: ['EGFR']
