Radioimmunotherapy: Recent results and future directions

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, 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 relative 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.