Treatment of multiple myeloma by antibody mediated immunotherapy and induction of myeloma selective antigens

Background: In view of the successful use of serotherapy in many B-cell mal ignancies, we and others have sought to identify tumor selective antigens f or the serotherapy of plasma cell dyscrasias (PCD) including multiple myelo ma (MM), and Waldenstrom's macroglobulinemia (WM). We recently identified M uc-1 core protein as a MM selective antigen. Though Muc-1 core protein is a bundantly expressed on most MM plasma cells, expression of this antigen can be absent, or weak on some plasma cells which could potentially result in the selection of Muc-1 core protein negative clones following serotherapy o f PCD. In addition to Muc-1 core protein, we have also been examining the u se of CD20 directed serotherapy for PCD. Design: As part of these efforts, we recently initiated a phase II clinical trial examining the use of Rituximab (Rituxan, MabThera) as a single agent in MM patients; as well several WM patients have been treated with Rituxim ab at our Institutions. Results: In previous studies, we have shown that CD20 is abundantly express ed on the plasma cells of most WM patients; in contrast, CD20 is expressed on plasma cells from a minority of MM patients, and in these patients expre ssion of CD20 can be weak or heterogeneous with both CD20+ and CD20- plasma cells present. As such, we have sought out clinically useful inducers of M uc-1 core protein, and of CD20 on malignant plasma cells. Conclusions: These efforts resulted in the identification of dexamethasone (Dex) as a potent inducer of Muc-1 core protein on MM plasma cells, and int erferon-gamma (IFN-gamma) as a potent inducer of CD20 on MM plasma cells an d B-cells. Importantly, these agents induced their respective antigens at p harmacologically achievable doses.