Avidin in the context of antibody-guided three-step therapies

Discovery of tumor specific antigens expressed at cancer cell surface led to the development of several immune-based strategies for the detection and the treatment of malignant pathologies. In this regard, the antibody-guided three-step therapy – also called “pretargeting strategy“ – offers interesting advantages for targeting cancer cells (Urbano et al., 2007; Goodwin and Meares 2001). In this kind of radioimmunotherapy, the first step consists to an administration of a biotinylated antibody raised against the tumor specific antigen followed, in the second step, by an avidin and/or streptavidin administration and, in the third step, by an injection of a radiolabeled biotine aimed at killing cancer cells. As compared to a strategy in which the antibody is directly linked to the radioelement, the avidin/biotin-based three-step therapy could offer a better tumor-to-nontumor ratio of the radioactivity accumulation because a clearance of non-specifically bound antibodies is possible between the first and the second step (Sakahara and Saga, 1999). Interestingly, in phase I–II clinical trials, using a biotinylated anti-tenascin monoclonal antibody (1st step), avidin and streptavidin (2nd step) and an yttrium 90 labelled biotine (3rd step), the three-step therapy appears to be a promising strategy for the treatment of patients with recurrent high grade glioma, ie grade III/IV glioma and glioblastoma (Paganelli et al., 1999; Grana et al., 2002).


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Grana C, Chinol M, Robertson C, Mazzetta C, Bartolomei M, De Cicco C, Fiorenza M, Gatti M, Caliceti P, Paganelli G. 2002. Pretargeted adjuvant radioimmunotherapy with yttrium-90-biotin in malignant glioma patients: a pilot study. Br J Cancer 86(2):207-12.
Paganelli G, Grana C, Chinol M, Cremonesi M, De Cicco C, De Braud F, Robertson C, Zurrida S, Casadio C, Zoboli S, Siccardi AG, Veronesi U. 1999. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin. Eur J Nucl Med 26(4):348-57.
Urbano N, Papi S, Ginanneschi M, De Santis R, Pace S, Lindstedt R, Ferrari L, Choi S, Paganelli G, Chinol M. 2007. Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT). Eur J Nucl Med Mol Imaging 34(1):68-77.
Sakahara H, Saga T. 1999. Avidin–biotin system for delivery of diagnostic agents. Adv Drug Deliv Rev 37(1-3):89-101.

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