T-CELL RETARGETING USING BISPECIFIC MONOCLONAL-ANTIBODIES IN A RAT COLON-CARCINOMA MODEL .4. TUMOR NEUTRALIZATION IN WINN TYPE ASSAYS

We investigated the ability of bispecific anti-T-cell receptor x anti-tumor antibodies, destined for the study of T-cell retargeting in a rat colon carcinoma model, to enhance tumor neutralization by polyclonally activated CD8+ T lymphocytes in hepatic subcapsular Winn type assays against syngeneic CC531 colon carcinoma cells. Attempts to improve on initially unsatisfactory results were guided by a 3-day in vitro cocultivation assay, demonstrating that recombinant IL-2 (rIL-2) at concentrations as low as 1 U/ml would promote tumor neutralization by retargeted effector cells. Accordingly, we found that a nontoxic regimen of rIL-2 administration, 200,000 U subcutaneously every 8 h for 3 days. strongly enhanced natural killer-like as well as retargeted anti-tumor activity in Winn assays and enabled retargeted effector cells to prevent tumor growth in the majority of animals. These results back up and direct future attempts to treat established tumor lesions.