Tumor Cell Targeting with Antibody-Avidin Complexes and Biotinylated Tumor Necrosis Factor α

摘要: Abstract Tumor pretargeting with biotinylated antibodies and avidin, followed by a delayed delivery of radioactive-labeled biotin, is currently used for in vivo diagnosis therapy cancer patients. Herein, we describe the use three-step antibody/avidin targeting approach to increase local concentration persistence human tumor necrosis factor α (bio-TNF) on mouse tumor. Mouse RMA lymphoma cells were transfected Thy 1.1 allele ( RMA-Thy ) generate unique tumor-associated antigen. In vitro anti-Thy monoclonal antibody 19E12 (bio-19E12) NeutrAvidin increased amount bio-TNF that bound cell (10–20 times comparison non-pretargeted cells), as well its half-life surface (> 30 times). Furthermore, reduced more than 2 orders magnitude LD 50 cytolytic assay actinomycin D. Finally, cells, pretreated according procedure injected into syngeneic C57/BL6 mice, less tumorigenic controls. These results indicate markedly increases cell-bound can trigger effects antitumor . avidin could be novel strategy increasing therapeutic index TNF.