Monoclonal Antibodies

Rituximab was the first humanized monoclonal antibody to be widely used in the treatment of patients with low- and intermediate-grade B-cell NHL. Subsequently, antibodies directed against a variety of epitopes have been developed and have demonstrated clinical efficacy. Unmodified anti-CD22 antibody as well as immunotoxin and radioimmunoconjugates of this antibody have demonstrated activity in vitro and in a limited number of patients with refractory B-cell lymphoma.1-3 CD30, which is expressed on a subset of T-cell lymphomas, including anaplastic large cell lymphomas and Hodgkin's disease, has been an attractive target for antibody-based therapies because its expression is limited on normal cells to activated lymphocytes and natural killer cells. SGN-30, a humanized anti-CD30 antibody, has been shown to induce growth arrest and apoptosis in Hodgkin's cell lines in vitro, and a phase II clinical trial is underway to further define its clinical efficacy.4 Alemtuzumab (Campath-1H) is a humanized mAb targeting CD52 and has recently been approved in the United States for the treatment of fludarabine-refractory B-cell chronic lym-phocytic leukemia. Impressive activity has also been demonstrated in T-cell prolymphocytic leukemia and mycosis fungoides.5 In a study of 16 patients with low-or intermediate-grade B-cell NHL who relapsed or were refractory to conventional therapy and were treated with alemtuzumab, eight (44%) achieved a clinical response, two (11%) had stable disease, and five (28%) had progressive disease. All responders had low-grade histologies.6 Humanized anti-CD4 antibody (HuMax) is used in clinical trials in patients with relapsed and refractory cutaneous T-cell lymphoma (CTCL) and CD4-expressing peripheral T-cell lymphomas.

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