title: Direct effect of rituximab in B-cell-derived lymphoid neoplasias: mechanism, regulation, and perspectives.
abstract: The anti-CD20 monoclonal antibody rituximab is the backbone of treatment for the B-cell malignancies non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, there is a wide variability in response to rituximab treatment, and some patients are refractory to current standard therapies. Rituximab kills B cells by multiple mechanisms of action, including complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which are immune-mediated mechanisms, as well as by direct effects on cell signaling pathways and cell membranes following CD20 binding. A large number of events that are affected by rituximab binding have been identified, including lipid raft modifications, kinase and caspase activation, and effects on transcription factors and apoptotic/antiapoptotic molecules. Studies on cell lines and isolated tumor cells have shown that by targeting these pathways, it may be possible to increase or decrease susceptibility to rituximab cell killing. An increased understanding of the direct effects of rituximab may therefore aid in the design of new, rational combinations to improve the outcome of CD20-based therapy for patients who currently have suboptimal outcome following standard treatments.
authors.affiliation: Cancer Research Center of Toulouse, CHU Purpan, Place du Dr Baylac, Toulouse, 31024 France. christine.bezombes-cagnac@inserm.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Bezombes
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab