Mechanism of action of rituximab.
The CD20 antigen is strongly and stably expressed on cells of the B-cell lineage, but not on stem cells, and is thus an ideal target antigen for antibody therapy of B-cell malignancies. Rituximab is a human-mouse chimeric monoclonal antibody to the CD20 antigen that kills B-cells by a number of different effector mechanisms. The human IgG component of the antibody is able to bind human complement and also interact with effector cells to kill cells by antibody-dependent cell-mediated cytotoxicity. Some investigators have also shown direct effects of the antibody on human tumor cell lines expressing CD20. These effects include inhibition of proliferation, induction of apoptosis and increased sensitivity to chemotherapeutic agents, although the extent to which each of these mechanisms may contribute to the anti-tumor action of rituximab remains to be determined. Rituximab thus acts by additional mechanisms compared to conventional chemotherapeutic agents. The chimeric nature of the antibody results in minimal immunogenicity and allows repeat use. The antibody may be combined with conventional chemotherapy, with potential for increased efficacy with minimal added toxicity.
Maloney
D G
DG
Fred Hutchison Cancer Research Center, Seattle, WA 98109, USA. dmaloney@fhcrc.org
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D000941:Antigens / Q000737:chemistry; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D011485:Protein Binding; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000941:Antigens; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D000069283:Rituximab