Advances in immunotherapy of hematologic malignancies: cellular and humoral approaches

Monoclonal antibodies have become an important modality for cancer therapy. Genetically engineered chimeric and humanized antibodies have demonstrated activity against overt lymphoma and leukemia, as well as minimal residual disease. Radioimmunotherapy in both nonmyeloablative and myeloablative regimens has produced significant responses and also minimized radiation exposure to normal tissues. Targeted alpha-particle therapy offers the possibility of selective tumor cell kill. Antibody-drug conjugates have produced remissions in acute leukemia. Many proteins potentially act as leukemia or lymphoma-specific antigens for major histocompatibility complex-restricted T cell cytotoxicity. These include the idiotype proteins, breakpoint cluster region (bcr)-abl and other fusion oncoproteins, myeloid-specific differentiation antigens and minor histocompatibility antigens. Clinical trials exploiting the new understanding of the T cell immunology are underway.