Rational Therapeutic Targets in Large B-Cell and Mantle Cell Lymphomas

The aggressive lymphomas are potentially curable. The natural history of certain aggressive lymphomas has been altered by monoclonal antibody therapy. Targeted monoclonal antibody therapy to the CD20 antigen has altered the outcome of patients with diffuse large B-cell lymphoma in patients of all ages. Anti-CD20–based radioimmunoconjugates are being evaluated as radioimmunotherapy approaches in patients who have relapsed and in stem cell transplant settings. Antibody-directed therapy to the B-cell– specific antigen CD22 are ongoing. New approaches include different CD20 antibodies and an antibody to the CD40 antigen, which is a member of the tumor necrosis factor (TNF) receptor family, which is expressed on B-cells. Antibody therapy has been incorporated into CHOP (cyclophosphamide, adriamycin, vincristine, prednisone) therapy and other regimens such as EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) and HyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone). Single-agent anti-CD20 therapy is active in the post-transplantation lymphoproliferative disorders. T-cell antibodies are under evaluation in a number of T-cell lymphoproliferative disorders. Targeted therapy has changed the natural history of a number of aggressive non-Hodgkin lymphomas. This review will describe the contributions of antibody therapies to the treatment of these diseases.