MAb therapy comes of age

sented summarizing the therapeutic uses of MAbs directed against CD20. Like many drugs, anti-CD20 MAbs have gone through the initial euphoria during development, to understanding that the high-placed hopes could never be realized, finally settling at more appropriate uses. With regulatory approval of rituximab for the treatment of patients with relapsed low-grade NHL, our arsenal gains a new and novel tool. The comprehensive review by Derigs describes the development of rituximab, as well as the basic biology underlying its use. A significant percentage of patients with relapsed low-grade lymphoma have clearly enjoyed clinical responses, some of which remain surprisingly durable. The utility of anti-CD20 Ab therapy in other clinical settings, such as the treatment of patients with recurrent intermediate-grade NHL, as well as the potential use of these agents in cleansing stem-cell products, is much less clear. Several groups are in the process of exploring the use of anti-CD20 MAbs following aggressive chemotherapy and autologous hematopoietic stem-cell transplantation. This would appear to be an ideal test of the potential efficacy of Ab therapy, since the majority of patients are rendered into complete remission following high-dose therapy, however, a significant percentage of patients will ultimately relapse. Clearly, well-performed prospective controlled randomized clinical trials are required to document the potential clinical efficacy of this therapeutic intervention. As with all drugs, possible side effects should be carefully monitored. The removal of CD20 cells, with the potential for immune dysfunction and dysregulation, must be assessed. To date, fortunately, anti-CD20 therapy has been relatively well-tolerated. However, the potential for long-term immunosuppression, infections and, in some instances, unexplained cytopenias must be rigorously evaluated and followed carefully. The eloquent review by Vose outlines the studies that have led to the approval of rituximab, as well as newer studies of patients with aggressive NHL following autologous stem-cell transplantation. It is clear that the use of unconjugated Abs is only the beginning. The different possible conjugates, including radionuclides, toxins, chemotherapy and other agents, is only limited by the imagination of the investigators. Several radiolabeled MAbs are nearing clinical approval, which could further aid in the treatment of diseases characterized by malignant cells expressing CD20. A major concern with the use of MAb therapy has been widespread clinical trials without validation. As with any useful therapeutic agent, multiple uses can be envisioned. Carefully constructed and executed clinical trials are required to determine whether these ideas are clinical realities. Other potential clinical uses, for example, the treatment of autoimmune diseases, ITP and other diseases of immune disregulation, will ultimately also be evaluated. There is little doubt that this is just the beginning, and lessons learned in the development and implementation of rituximab will be extremely valuable for the successful application of future Ab-based therapy. Cytotherapy (2001) Vol. 2, No. 6, 409