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Although thousands of patients have been treated with rituximab to date, researchers are just beginning to understand the basis on which this agent works. Rituximab is believed to induce tumor regression by several mechanisms of action, including antibody-dependent cellular cytotoxicity (ADCC), complement-mediated cytotoxicity (CDC), and induction of apoptosis. The mechanism by which apoptosis occurs also has not been clearly elucidated.

Obviously, scientific companion studies should be incorporated into appropriate clinical trials of rituximab. By determining the mechanism of action of the antibody, we may be able to enhance its activity and develop scientifically rational combinations with other drugs.

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