Specificity and biologic activities of novel anti-membrane IgM antibodies.

摘要: The concept that the B-cell Receptor (BCR) initiates a driver pathway in lymphoma-leukemia has been clinically validated. Previously described unique BCR Ig-class-specific sequences (proximal domains (PDs)), are not expressed serum Ig (sIg). As consequence of sequence and structural differences membrane IgM (mIgM) µ-Constant Domain 4, additional epitopes distinguish mIgM from sIgM. mAbs generated to linear conformational epitopes, restricted reacting with sIgM, were despite relative hydrophobicity PDm sequence. Anti-PD (mAb1, mAb2, mAb3) internalize mIgM. Anti-mIgM mAb4, which recognizes distinct non-ligand binding site epitope, mediates internalization, low-density cultures, growth inhibition, anti-clonogenic activity, apoptosis. We show mAb-mediated internalization generally does interrupt BCR-directed cell growth, however, mAb4 PDm-μC4 domain induces both anti-tumor effects. micro-clustering many leukemia lymphoma lines is demonstrated by SEM micrographs using these new mAb reagents. clinical candidate as mediator inhibition signaling pathway. agents do bind non-mIgM B-cells, nor cross-react non-lymphatic tissues, they may spare B-cell/normal tissue destruction mAb-drug conjugates.