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Experimental Therapeutics

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

Monica Moro, Micaela Pelagi, Giulia Fulci, Giovanni Paganelli, Paolo Dellabona, Giulia Casorati, Antonio G. Siccardi and Angelo Corti
Monica Moro
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Micaela Pelagi
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Giulia Fulci
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Giovanni Paganelli
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Paolo Dellabona
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Giulia Casorati
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Antonio G. Siccardi
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Angelo Corti
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DOI:  Published May 1997
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Abstract

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.

Footnotes

  • ↵1 This work was supported by Associazione Italiana Ricerca sul Cancro (AIRC). M. M. was recipient of a fellowship from AIRC.

  • ↵2 To whom requests for reprints should be addressed.

  • Received November 7, 1996.
  • Accepted March 24, 1997.
  • ©1997 American Association for Cancer Research.
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May 1997
Volume 57, Issue 10
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Tumor Cell Targeting with Antibody-Avidin Complexes and Biotinylated Tumor Necrosis Factor α
Monica Moro, Micaela Pelagi, Giulia Fulci, Giovanni Paganelli, Paolo Dellabona, Giulia Casorati, Antonio G. Siccardi and Angelo Corti
Cancer Res May 15 1997 (57) (10) 1922-1928;

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Tumor Cell Targeting with Antibody-Avidin Complexes and Biotinylated Tumor Necrosis Factor α
Monica Moro, Micaela Pelagi, Giulia Fulci, Giovanni Paganelli, Paolo Dellabona, Giulia Casorati, Antonio G. Siccardi and Angelo Corti
Cancer Res May 15 1997 (57) (10) 1922-1928;
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