NCIt definition : A humanized IgG4 monoclonal antibody that targets the human leukocyte antigen HLA-DR,
with potential antineoplastic activity. Upon administration, anti-HLA-DR monoclonal
antibody IMMU-114 binds to HLA-DR on HLA-DR-expressing tumor cells and, although the
exact mechanism has yet to be fully elucidated, appears to induce hyperactivation
of ERK- and JNK-dependent mitogen activated protein kinase signaling pathways. This
may lead to mitochondrial membrane depolarization and reactive oxygen species (ROS)
generation. This eventually leads to an induction of tumor cell apoptosis and a reduction
in tumor cell proliferation. IMMU-14 may be beneficial in the treatment of graft versus
host disease (GVHD) as it appears to suppress T-lymphocyte proliferation and natural
killer (NK) cell activation. As the Fc region of the orgnial IgG1 MoAb was replaced
with the IgG4 isotype, IMMU-114 does not induce a complement cytotoxicity (CDC) or
an antibody-dependent cell-mediated cytotoxicity (ADCC). HLA-DR, a MHC class II molecule,
is found on various b-cell hematologic malignancies and in autoimmune diseases as
well as on normal cells.;