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Immunology |
Departments of 1 Physiology and Pathology, 2 Biological Sciences, and 3 Biology, University of Trieste, Trieste, Italy; 4 Department of Human Pathology, University of Palermo, Palermo, Italy; and 5 Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy
Requests for reprints: Francesco Tedesco, Department of Physiology and Pathology, University of Trieste, via Fleming 22, 34127 Trieste, Italy. E-mail: tedesco{at}units.it.
An in vivo model of human CD20+ B-lymphoma was established in severe combined immunodeficiency mice to test the ability of human neutralizing miniantibodies to CD55 and CD59 (MB55 and MB59) to enhance the therapeutic effect of rituximab. The miniantibodies contained single-chain fragment variables and the hinge-CH2-CH3 domains of human IgG1. LCL2 cells were selected for the in vivo study among six B-lymphoma cell lines for their high susceptibility to rituximab-dependent complement-mediated killing enhanced by MB55 and MB59. The cells injected i.p. primarily colonized the liver and spleen, leading to the death of the animals within 30 to 40 days. Thirty percent of mice receiving biotin-labeled rituximab (25 µg) i.p. on days 4 and 11 after cell injection survived to 120 days. Administration of biotin-labeled rituximab, followed by avidin (40 µg) and biotin-labeled MB55–MB59 (100 µg) at 4-h intervals after each injection resulted in the survival of 70% of mice. Surprisingly, 40% of mice survived after the sole injection of avidin and biotin-labeled MB55–MB59, an observation consistent with the in vitro data showing that the miniantibodies induced killing of 
25% cells through antibody-dependent cell cytotoxicity. In conclusion, MB55 and MB59 targeted to tumor cells represent a valuable tool to enhance the therapeutic effect of rituximab and other complement-fixing antitumor antibodies. [Cancer Res 2007;67(21):10556–63]
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