Superior Activity of Fusion Protein scFvRit:sFasL over Cotreatment with Rituximab and Fas Agonists

摘要: The clinical efficacy of the CD20-specific chimeric monoclonal antibody rituximab is significantly hampered by intrinsic or acquired resistance to therapy. Rituximab activates antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity-dependent lysis but also induces apoptosis cross-linking its target antigen CD20. Recent reports indicate that this apoptotic activity can be synergized cotreatment with Fas agonists. Here, we report on a strategy designed exploit and optimize synergy between signaling genetically fusing rituximab-derived fragment soluble ligand (sFasL). resultant fusion protein, designated scFvRit:sFasL, potently induced CD20-restricted in panel malignant B-cell lines (10 11) primary patient-derived B cells (two two non-Hodgkin lymphoma five six cell chronic lymphocytic leukemia). ScFvRit:sFasL efficiently activated CD20 signaling, resulting far superior proapoptotic compared lacked toward normal human systemic toxicity nude mice no elevation aspartate aminotransferase alanine levels liver caspase-3 activity. In conclusion, scFvRit:sFasL Fas-apoptotic may useful for elimination cells.