IN-VIVO MODULATORS OF ANTIBODY KINETICS

The aim of the present study was to summarize the effect of in vivo mo dulation of antibody kinetics and to present new data on the in vivo e ffect of the cell membrane active detergent Tween 80 and the cytokine interleukin-2 (IL-2) on the accumulation and clearance of a radioactiv e antibody, Mice bearing Lewis lung carcinoma xenografts and rats bear ing DMBA-induced mammary carcinomas were studied after injecting I-125 labeled IgG(1) monoclonal antibody (3c4c7g6) raised against a tyrosin e kinase receptor protein Tie, Expression of Tie is known to be abunda nt in vascular endothelia and possibly related to malignant angiogenes is, Tween 80 was administered intratumorally (0.04% of tumor volume), whereas IL-2 was administered intraperitoneally. In the Lewis lung tum or model, the absolute tumor uptake varied between 2 and 5% ID/g, and maximum uptake was achieved after 24 h with Tween, and after 48 h with out Tween, Tween manipulation did not increase the uptake in any norma l organ, but it enhanced antibody clearance from the blood, In the DMB A rat model, IL-2 had no effect on blood clearance, but enhanced the u ptake of Tie antibody into the tumor from 2.5-0.9 to 4.5-0.4% ID/g at 48 h, These data indicate that antibody biodistribution and pharmacoki netics can be modulated by a surface detergent and a cytokine, giving decreased exposure to critical organs, and increased uptake into the t umor, This type of manipulation provides an opportunity to optimize ra dio-immunotherapy.