[Development of monoclonal antibody therapy for malignant lymphoma]

Lymphomas are among the tumors most responsive to chemotherapeutic agents and radiation therapy. Despite chemotherapeutic and radiological advances, tumor cell resistance still remains a problem, and the toxicity of chemotherapy and radiation therapy limits their potential. Less toxic therapies for lymphoma have been continued to search for effectiveness. Since the discovery of the hybridoma technology by Kohler and Milstein in 1975, utilizing antibodies as targeted therapy for lymphoma has been investigated for many years. After 20 years of clinical trials, monoclonal antibody therapy of lymphoma enters the new millennium ready for 'prime time'. Investigators' early enthusiasm was dampened by problems with tumor targeting, HAMA, and allergic reactions, but important advances in molecular biology and chelation chemistry have led to new and improved reagents. Rituximab(IDEC-C2B8) has already been approved by the FDA in USA and the Ministry of Welfare and Labour in Japan for relapsed CD20-positive lymphomas and indolent B-cell lymphoma including mantle cell lymphoma, respectively. Ibritumomab tiuxetan and iodine-131 anti-B1 antibody have an excellent anti-lymphoma profile, and both appear to have higher response rates than rituximab. Results from the rituximab vs. ibritumomab tiuxetan phase III trial clearly favor the latter especially in %CR. Radiolabeled Lym-1, T101, LL2, and anti-Tac data will be forthcoming. Continued refinements of immunotoxins will establish their possible therapeutic role, and a variety of antibody conjugates including drugs, prodrugs, nonprotein toxins, and other agents, will continue to be studied in the clinic. Bispecific antibodies for lymphoma are also in early clinical testing. Over the next 10 years, many of the major advances in lymphoma therapy will be antibody-based.