The antileukemia activity of a human anti-CD40 antagonist antibody, HCD122, on human chronic lymphocytic leukemia cells

摘要: B-cell chronic lymphocytic leukemia (B-CLL) is a lymphoproliferative disorder characterized by the surface expression of CD20, CD5 antigens, as well receptor CD40. Activation CD40 its ligand (CD40L) induces proliferation and rescues cells from spontaneous chemotherapy-induced apoptosis. activation also secretion cytokines, such IL-6, IL-10, TNF-alpha, IL-8, GM-CSF, which are involved in tumor cell survival, migration, interaction with microenvironment. Here we demonstrate that primary B-CLL cells, novel antagonist anti-CD40 monoclonal antibody, HCD122, inhibits CD40L-induced signaling pathways, cytokines. Furthermore, HCD122 potent mediator antibody-dependent cellular cytotoxicity (ADCC), lysing more efficiently than rituximab vitro, despite significantly higher number CD20 binding sites compared Unlike rituximab, however, (formerly CHIR-12.12) does not internalize upon to cells. Our data suggest may inhibit growth blocking ADCC-mediated lysis.