Rituximab and other emerging antibodies as molecular target-based therapy of lymphoma.

Among the monoclonal antibodies (mAbs) under clinical development, anti-CD20 mAbs have been most extensively investigated and have shown definitive clinical activities. Rituximab is a genetically engineered, chimeric anti-CD20 mAb with mouse variable and human constant regions. Consecutive clinical trials conducted in the United States, Europe, and Japan have revealed that rituximab is an effective agent, with acceptable toxicities, in the treatment of indolent and aggressive B-cell non-Hodgkin's lymphomas (B-NHLs). A recent European phase III study in elderly patients with untreated diffuse large B-cell lymphoma suggested that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy is superior to CHOP chemotherapy alone in terms of complete response rate and event-free and overall survivals. Lymphoma is inherently a radiosensitive tumor. The aim of radioimmunotherapy is to use the mAb to target radiation to lymphoma tissue while minimizing toxicity to normal cells. Clinical trials of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab showed that they have definitive efficacy in relapsed indolent B-NHL, with acceptable toxicities. A recent comparative study in relapsed indolent B-NHL showed that (90)Y-ibritumomab tiuxetan produced a higher response rate than rituximab. In addition, BL22, a recombinant anti-CD22 immunotoxin, showed significant efficacy in patients with chemotherapy-resistant hairy cell leukemia. Monoclonal antibodies will have significant roles in the treatment of lymphoid malignancies in the future.