PT  - JOURNAL ARTICLE
AU  - Moro, Monica
AU  - Pelagi, Micaela
AU  - Fulci, Giulia
AU  - Paganelli, Giovanni
AU  - Dellabona, Paolo
AU  - Casorati, Giulia
AU  - Siccardi, Antonio G.
AU  - Corti, Angelo
TI  - Tumor Cell Targeting with Antibody-Avidin Complexes and Biotinylated Tumor Necrosis Factor α
DP  - 1997 May 15
TA  - Cancer Research
PG  - 1922--1928
VI  - 57
IP  - 10
4099  - http://cancerres.aacrjournals.org/content/57/10/1922.short
4100  - http://cancerres.aacrjournals.org/content/57/10/1922.full
SO  - Cancer Res1997 May 15; 57
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.