Radioimmunotherapy: recent results and future directions.

Abstract

PURPOSE To review antibody structure, function, and production; suitable radioisotopes for radioimmunotherapy; challenges facing the field; recent clinical results; toxicity; and future directions. DESIGN The radioimmunotherapy literature was reviewed, with an emphasis on clinical results and future directions. RESULTS The highest complete response rates (overall, approximately 50%) have been achieved in patients with B-cell non-Hodgkin's lymphoma. Challenges that currently face radioimmunotherapy include circulating free antigen, binding of antibodies to nonspecific Fc receptors, insufficient tumor penetration, antigenic heterogeneity and insufficient antigen expression, antigenic modulation, and development of human antimouse antibodies. Possible approaches to these challenges, including high-dose radioimmunotherapy and chemotherapy followed by autologous bone marrow transplantation, the use of radionuclides such as yttrium 90 (90Y) and copper 67 (67Cu), and the development of humanized and bifunctional antibodies, are under investigation. CONCLUSION Although radioimmunotherapy is a relatively new field, substantial progress has been made. Additional research will ultimately resolve many of the challenges that currently face radioimmunotherapy and hopefully lead to the cure of some currently incurable malignancies.