Rituximab (brand name MABTHERA) is a monoclonal antibody that binds to CD20 B cells causing lysis of cells positive antigene. Rituximab binds specifically to the transmembrane CD20 antigene, non-glycosylated phosphoprotein located on pre-B lymphocytes and mature B Lymphocytes.
The antigene is expressed on more than 95% of all non-Hodgkin B cell (NHLs) lymphomas. CD20 is found in normal and malignant B cells, but not in hematopoietic stem cells, pro-B cells, normal plasma cells or other normal tissues. The antigene is not internalized upon antibody binding and it’s not shed from the cell surface.
CD20 doesn’t circulate in blood as free antigene and thus does not compete for antibodie binding.
The Fab domain of Rituximab binds to CD20 antigene on B lymphocytes and activates immune effector functions in order to cause lysis of B cells via the Fc domain. possible mechanisms of Cell lysis include complement-dependent cytotoxicity (CDC) by binding to C1q and antibody-dependant cellular cytotoxicity (ADCC) mediated by one or more Fc receptors g on the surface of granulocytes, macrophages and NK cells.
The drug is already approved for the treatment of patients with follicular lymphoma stage III-IV chemoresistant or in their second or subsequent relapse after chemotherapy, for the treatment of patients with non-Hodgkin’s lymphoma, CD20 positive diffuse large B cell, in combination with CHOP chemotherapy and finally for the treatment of patients with follicular lymphoma stage III-IV previously un treated, in combination with CVP chemotherapy. It was now approved by the EMEA for the maintainance treatment of patients with relapse/refractory follicular lymphoma who respond to induction therapy with chemotherapy with or without Rituximab in combination with methotrexate for the treatment of rheumatoid arthritis treatment active severe in patients who have had an inadequate response or intolerance to other disease-modifying antirheumatic drug therapy, including one or more drugs inhibiting tumor necrosis factor (TNF). The median peripheral B cell counts declined below normal following the first dose, with the beginning of recovery after 6 months.
Normal levels of B cells were obtained between 9 and 12 months following the end of treatment.
The development of inhibitors of protein farnesyl transferase, such as R115777 and lonafarnib, is derived from the observation that the ras protein to acquire its biological properties, must be activated by farnesyl transferase. In a phase I study administration of R115777 in patients with advanced solid tumors has been effective. The antineoplastic activity of lonafarnib was evaluated in phase I studies, either alone or in combination with chemotherapy, with good tolerability and efficacy.