Radioimmunotherapy of hematological cancer: problems and progress.

Introduction The optimistic and naive view of the early l980s that mAbs2 were ‘ ‘ magic bullets’ ‘ has now been replaced by a more realistic understanding of the many obstacles to their effective use. Although some mAbs have produced significant antitumor responses in humans (1-6), a number of factors, including the weak cytotoxic activity of many murine mAbs. the difficulty in delivering mAbs to bulky disease, and the heterogeneity of antigen expression on tumor cells, have limited their utility. Because host effector mechanisms are not required for tumor cell killing, radioimmunotherapy has become a promising approach for the treatment of cancer. The use of radiolabeled mAbs may also partly overcome the problems of mAb penetration into solid masses and antigen heterogeneity, since cells in proximity to bound antibody may be killed by exposure to the local radiation field. Some of the most encouraging results using radioimmunotherapy have been seen in hematological neoplasms. These diseases are ideally suited to the study of mAb therapies because of the accessibility of malignant cells in the blood, bone marrow, spleen, and lymph nodes. Additionally, the well-defined immunophenotypes of the various lineages and stages of hematopoietic differentiation have allowed antigenic targets to be identified (Table I). In this review, we consider the various issues that can affect the outcome of therapy with radiolabeled mAbs and examine new areas of investigation to improve therapeutic results. We then discuss some of the recent clinical trials for non-Hodgkin’s lymphoma and leukemia using radioimmunoconjugates.