Monoclonal Antibody Therapy For Hematologic Malignancies

Monoclonal antibodies are a new class of agents that target tumor-associated antigens. Advances in hybridoma technologies in the early 1980s allowed the creation of monoclonal antibodies with high specificity in addition to the development of monoclonal antibodies that can be linked to anticancer drugs, radioisotopes, or toxins. Several cancer-specific monoclonal antibodies have received approval by the United States Food and Drug Administration (FDA) and many more are currently under clinical investigation. This review summarizes the monoclonal antibodies either approved by the FDA or in development for the treatment of hematologic malignancies. Rituximab, which targets the CD20 antigen, has revolutionized the treatment of B-cell lymphoma. The standard of care for front-line treatment of follicular center cell lymphoma and diffuse large B-cell lymphomas, which are the predominate two lymphomas in the Western world, is rituximab combined with chemotherapy. Second-generation anti-CD20 monoclonal antibodies are currently being studied in phase II and III trials. Radioimmunotherapy with anti-CD20 antibodies has also been approved by the FDA for the second-line treatment of follicular lymphoma. Additional antibodies and immunocongugates targeting a variety of B-cell-associated antigens are also in the clinic for hematologic malignancies including antibodies targeting CD22, CD23, CD80, CD40, CD30, CD4, CD37, CD74, CTLA-4, VEGF, and the insulin-like growth factor I receptor. We believe that many of these monoclonal antibodies and immunoconjugates will become standard of care for a variety of hematologic malignancies.