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.