THE USE OF DAUNOMYCIN-ANTIBODY IMMUNOCONJUGATES IN MANAGING SOFT-TISSUE SARCOMAS - NUDE-MOUSE XENOGRAFT MODEL

Analysis of human fibrosarcoma cells exposed to radiolabeled monoclona l antibody 19-24, which recognizes sarcoma-associated antigen p102, re vealed that over 54% of the cell surface-bound radioactivity was inter nalized. No modulation of cell surface p102 antigen by monoclonal anti body 19-24 was observed in human fibrosarcoma cells. Monoclonal antibo dy 19-24 coupled to daunomycin via a dextran bridge was found to be mo st effective. In different preparations, the daunomycin:total protein molar ratio ranged from 1.9 to 6.1. In vitro cytotoxicity studies usin g human fibrosarcoma cells showed that, at 10 mug/ml concentration, th is immunoconjugate was 79.4% as efficient as free daunomycin and, at 1 mug/ml concentration, 36.8% as efficient. Control nonspecific murine monoclonal antibody P3 immunoconjugates were relatively ineffective. T he distribution of C-14-Adriamycin, I-125-labeled monoclonal antibody 19-24, and I-125-labeled 19-24 immunoconjugate was also evaluated over a 24-h period in tumor and normal tissues of athymic mice bearing a h uman fibrosarcoma xenograft. Poor uptake of radiolabeled Adriamycin by the tumor tissue was observed. The level of C-14 radioactivity in the tumor tissue never exceeded 1% of the total injected dose and was 24. 8-fold lower than the radioactivity found in the spleen tissue. Tumor tissue uptake of radiolabeled monoclonal antibody 19-24 was characteri zed by the high tumor tissue:blood ratio of 1.62 +/- 0.28 (SD). Howeve r, for monoclonal antibody 19-24 immunoconjugates, this ratio decrease d to 0.66 +/- 0.05, which was still higher than normal (liver, 0.48 +/ - 0.02; lung, 0.48 +/- 0.07; spleen, 0.28 +/- 0.01) or nonspecific mon oclonal antibody P3 immunoconjugates (0.22 +/- 0.03). Thus, it appears that, compared to free daunomycin, monoclonal antibody 19-24 immunoco njugates may be more efficient and less cytotoxic to normal tissues.