Adoptive immunotherapy by avidin-driven cytotoxic T lymphocyte-tumor bridging

We have shown previously that T cells, tagged with biotinylated anti-CD3 an tibody fragments, can exert avidin-dependent cytolytic activity on suitably biotinylated tumor cells in vitro. In this study, we demonstrate that avid in-driven CTL-tumor bridging in vivo leads to growth inhibition of murine t umors WEHI-164 fibrosarcoma and RMA Lymphoma. The biodistribution of biotin -tagged In-111-labeled T cells demonstrated a selective avidin-dependent an d time-dependent accumulation of radioactivity at tumor sites, The specific ity of lymphocyte tumor localization was demonstrated by the concurrent tim e-dependent decrease of radioactivity in the blood and in all other organs, Furthermore, we documented a therapeutic effect of the adoptively transfer red 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 lo calization and no delay in tumor growth, indicating that avidin bridging wa s essential for T-cell activity at tumor sites.