An overview of monoclonal antibody therapy of cancer

Monoclonal antibody-based therapeutics are beginning to realize the promise that was predicted with the advent of the core technology more than 20 years ago. Antibody-based therapeutics targeting tumor cell surface antigens such as B-cell idiotypes, CD20 on malignant B cells, CD33 on leukemic blasts, and HER2/neu on breast cancer cells have shown efficacy in clinical trials. Multiple antibody-based strategies have shown promising efficacy in recent clinical trials. Unconjugated immunoglobulins directed against CD20 induce partial and complete responses in up to 50% of patients with advanced, indolent non-Hodgkin's lymphoma When such antibodies are conjugated to appropriate radionuclides and administered in therapeutic doses, the proportions of complete and overall responses increase considerably. Conjugates composed of anti-CD33 antibodies and the chemotherapy agent, calicheamicin, show promising activity in patients with relapsed or refractory acute myelogenous leukemia. Treatment of patients with advanced breast cancer using the anti-HER2/neu antibody trastuzumab (Herceptin; Genentech, San Francisco) leads to objective responses in some patients whose tumors overexpress the HER2/neu oncoprotein. These exciting results justify recent enthusiasm for continued efforts to refine existing approaches and to develop new antibody-based strategies to treat human malignancy.