A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy

摘要: Many tumors, including lymphomas, up-regulate expression of CD46 to escape destruction by complement. Tumor cells are therefore relatively resistant therapy monoclonal antibodies, which act through complement-dependent cytotoxicity (CDC). From an Escherichia coli library adenovirus type 35 fiber knob mutants, we selected a variant (Ad35K++) that had higher affinity than did the natural Ad35 knob. We demonstrated incubation lymphoma with recombinant Ad35K++ protein resulted in transient removal from cell surface. Preincubation sensitized CDC, triggered CD20-specific antibody rituximab. In xenograft models human cells, preinjection dramatically increased therapeutic effect Blood counts and organ histology were normal after intravenous injection into mice express CD46. The presence polyclonal anti-Ad35K++ antibodies not affect ability enhance rituximab-mediated CDC vitro assays. Ad35K++-based approach has potential implications malignancies beyond combination