Molecular cloning and characterization of a surface antigen preferentiallyoverexpressed on multiple myeloma cells

HM1.24 antigen has been identified as a surface molecule preferentially exp ressed on terminally differentiated B cells, and its overexpression is obse rved in multiple myeloma cells. The HM1.24 antigen is, therefore, expected as a most potent target molecule for antibody-based immunotherapy for multi ple myeloma. Here, we have identified the cDNA for human HM1.24 antigen and also analyzed its gene structure including the promoter region. The HM1.24 antigen is a type II membrane glycoprotein, which has been reported as a b one marrow stromal cell surface antigen BST2, and may exist as a homodimer on myeloma cell surface. Although a reason for the overexpression in myelom a cells is not understood, very interestingly, the promoter region of the H M1.24 gene has a tandem repeat of three cis elements for a transcription fa ctor, STAT3, which mediates interleukin-6 (IL-6) response gene expression. Since IL-6 is a differentiation factor for B cells, and known as a paracrin e/autocrine growth factor for multiple myeloma cells, the expression of HM1 .24 antigen may be regulated by the activation of STAT3. Importantly, a hum anized anti-HM1.24 antibody effectively lysed the CHO transformants which e xpressed HM1.24 antigen as high as human multiple myeloma cells, but not th e cells with lower antigen expression. This evaluation shows that ADCC heav ily depends on the expression level of target antigens and, therefore, the immunotherapy targeting the HM1.24 antigen should have a promising potentia l in clinical use. (C) 1999 Academic Press.