RT Journal Article
SR Electronic
T1 Tumor Cell Targeting with Antibody-Avidin Complexes and Biotinylated Tumor Necrosis Factor α
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1922
OP 1928
VO 57
IS 10
A1 Moro, Monica
A1 Pelagi, Micaela
A1 Fulci, Giulia
A1 Paganelli, Giovanni
A1 Dellabona, Paolo
A1 Casorati, Giulia
A1 Siccardi, Antonio G.
A1 Corti, Angelo
YR 1997
UL http://cancerres.aacrjournals.org/content/57/10/1922.abstract
AB Tumor pretargeting with biotinylated antibodies and avidin, followed by a delayed delivery of radioactive-labeled biotin, is currently used for in vivo diagnosis and therapy in cancer patients. Herein, we describe the use of a three-step antibody/avidin targeting approach to increase the local concentration and the persistence of biotinylated human tumor necrosis factor α (bio-TNF) on a mouse tumor. Mouse RMA lymphoma cells were transfected with the Thy 1.1 allele (RMA-Thy 1.1) to generate a unique tumor-associated antigen. In vitro pretargeting of RMA-Thy 1.1 cells with the biotinylated anti-Thy 1.1 monoclonal antibody 19E12 (bio-19E12) and NeutrAvidin increased the amount of bio-TNF that bound to the cell (10–20 times in comparison with non-pretargeted cells), as well as its half-life on the surface (> 30 times). Furthermore, cell pretargeting reduced by more than 2 orders of magnitude the LD50 of bio-TNF in a cytolytic assay with actinomycin D. Finally, RMA-Thy 1.1 cells, pretreated in vitro with bio-TNF according to the three-step procedure and injected into syngeneic C57/BL6 mice, were less tumorigenic than controls. These results indicate that the three-step targeting approach markedly increases the amount and the persistence of bio-TNF on the cell surface and that cell-bound bio-TNF can trigger cytolytic effects in vitro and antitumor effects in vivo. Tumor pretargeting with biotinylated antibodies and avidin could be a novel strategy for increasing the therapeutic index of TNF. ©1997 American Association for Cancer Research.