Rituxan was the first monoclonal antibody that was approved by the US FDA for the treatment of cancer in 1997. Rituxan is a chimeric mAb (34% mouse protein and 66% human protein) and is directed against B-lymphocyte-restricted differentiation antigen CD20. It has been developed by transferring the entire Fab domain of mouse anti-CD20 antibody to the human IgG1 framework (Hainsworth, 2000).
CD-20 antigen is expressed on the surface of more than 90% of B-cell non-Hodgkin's lymphomas (NHLs), on pre-B lymphocytes and on mature lymphocytes, but not on stem cells, plasma cells and other normal tissues. B-cell lymphoma accounts for 95% of all lymphomas.
Rituxan is jointly marketed by two American companies (IDEC Pharmaceutical and Genentech, California) for short-course outpatient treatment of relapsed or refractory CD20-positive, low-grade or follicular B-cell NHL. Rituxan is a less toxic alternative to chemotherapy and can induce anti-cancer activity by binding to CD20-positive cells, inducing apoptosis, recruiting immune effector functions (i.e. mediating ADCC) and activating complement (Scott, 1998; Hainsworth, 2000). As a single agent, rituximab has been shown to produce a response rate of 50% in patients with relapsed low-grade and follicular NHL. When added to standard chemotherapy in patients with diffuse, large, B-cell NHL, it has also been able to prolong survival in such patients (Dearden, 2002). Treatment-related toxicity, which occurs most often with the first infusion of the antibody, is generally mild. Infusion-related reactions included rigors, nausea, urticaria, fatigue and headache (Dillman, 2002). One advantage of Rituxan therapy is that, as it induces minimal adverse effects, it can be given to patients as short-course, outpatient therapy (375 mg/m2 weekly for 4-8 weeks). Further clinical trials examining the clinical benefits of adding Rituxan to conventional chemotherapy, using different schedules, are currently under way (Dearden, 2002; Foran, 2002).
The mAbs epratuzumab and apolizumab, which are directed against two different antigens CD22 and HLD-DR respectively, are also under clinical investigation for use in NHL (Leonard and Link, 2002). Simultaneous targeting of CD20, CD22 and HLA-DR antigens in patients with NHL by antibodies may produce a better therapeutic benefit in such patients, compared with those who are treated with one antibody. Further clinical trials in patients with NHL, with a combination of Rituxan, epratuzumab and apolizumab, should unravel the full potential of such strategies.
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