ABSTRACT

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of neoplastic plasma cells mainly in the bone marrow. This disease causes clinical symptoms resulting from end-organ damage such as anemia, destructive bone lesions, renal impairment, and immunodeciency. The introduction of chemotherapy and hematopoietic stem cell transplantation has improved overall survival, but unfortunately, MM remains incurable in most patients. Basic and clinical studies have provided new insights into the mechanism of MM pathogenesis within MM cells and the relationship between the tumor and the bone marrow microenvironment. Novel therapeutic agents such as thalidomide, lenalidomide, and bortezomib have been shown to signicantly improve patient outcomes. These agents have multiple biologic activities against both MM cells and the bone marrow microenvironment, and combination therapy has emerged as a promising treatment paradigm. Additionally, numerous efforts have been made to identify fundamental molecular targets and establish more specic therapy by using biologic agents such as cytokines, monoclonal antibodies (mAbs), and vaccines. This review summarizes the key

Abstract .................................................................................................................. 267 Construction of Therapeutic Monoclonal Antibodies ............................................268 Monoclonal Antibody Therapy for Hematological Malignancies .........................269 Target Antigens for Monoclonal Antibody Therapy of Multiple Myeloma ........... 270

Growth Factors and Signal Transduction Pathways .......................................... 270 Cell Surface Antigens and Adhesion Molecules ............................................... 273

Conclusion and Future Directions ......................................................................... 275 References .............................................................................................................. 275

issues of mAb therapy and the recent advances in the development of therapeutic mAbs for MM and plasma cell disorders.