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Adoptive Immunotherapy by Avidin-driven Cytotoxic T Lymphocyte- Tumor Bridging¹

Department of Biological and Technological Research [M. G., F. G., E. R., A. C., A. G. S.] and Unit of Biostatistics [F. V.], San Raffaele Scientific Institute, European Institute of Oncology [M. C., G. P.], and Department of Biology and Genetics, University of Milano [E. R., G. V., A. G. S.], I-20132 Milan, Italy

We have shown previously that T cells, tagged with biotinylated anti-CD3 antibody fragments, can exert avidin-dependent cytolytic activity on suitably biotinylated tumor cells in vitro. In this study, we demonstrate that avidin-driven CTL-tumor bridging in vivo leads to growth inhibition of murine tumors WEHI-164 fibrosarcoma and RMA lymphoma. The biodistribution of biotin-tagged ¹¹¹In-labeled T cells demonstrated a selective avidin-dependent and time-dependent accumulation of radioactivity at tumor sites. The specificity of lymphocyte tumor localization was demonstrated by the concurrent time-dependent decrease of radioactivity in the blood and in all other organs. Furthermore, we documented a therapeutic effect of the adoptively transferred T cells, i.e., a significant delay of tumor growth at early stages. All of the experiments included a control group of mice, which received all of the reagents, except avidin. These avidin-minus mice showed no specific localization and no delay in tumor growth, indicating that avidin bridging was essential for T-cell activity at tumor sites.

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