Monoclonal antibodies in the treatment of hematopoietic malignancies.

Overview

The development of practical methods for producing specific, highly purified monoclonal antibodies (MoAbs) targeted to specific tumor-cell antigens has opened new vistas in therapy for both hematologic malignancies and solid tumors. Numerous phase I trials with first-generation MoAbs have revealed both the broad therapeutic promise of MoAbs in anticancer therapy and the obstacles that must be overcome before they can be utilized fully in the clinical setting. MoAbs can be used to activate or manipulate the patient's immune system to destroy malignant cells. They also can be used as carriers for antitumor agents such as chemotherapeutic compounds, radiation, and toxins. Because many MoAbs are prepared from mouse cells, a common problem has been the development of resistance to the heterologous mouse protein. Strategies to circumvent this resistance include the use of human MoAbs, the production of chimeric mouse-human MoAbs, and the induction of tolerance to the mouse MoAbs. The possibility of combination therapy using MoAbs in conjunction with chemotherapy, lymphokines, or other biological response modifiers also is being explored.