Analysis of human
fibrosarcoma cells exposed to radiolabeled
monoclonal antibody 19-24, which recognizes
sarcoma-associated antigen p102, revealed that over 54% of the cell surface-bound radioactivity was internalized. No modulation of cell surface p102
antigen by
monoclonal antibody 19-24 was observed in human
fibrosarcoma cells.
Monoclonal antibody 19-24 coupled to
daunomycin via a
dextran bridge was found to be most effective. In different preparations, the
daunomycin:total
protein molar ratio ranged from 1.9 to 6.1. In vitro cytotoxicity studies using human
fibrosarcoma cells showed that,
at 10 micrograms/ml concentration, this
immunoconjugate was 79.4% as efficient as free
daunomycin and, at 1 microgram/ml concentration, 36.8% as efficient. Control nonspecific murine
monoclonal antibody P3
immunoconjugates were relatively ineffective. The distribution of 14C-Adriamycin, 125I-labeled
monoclonal antibody 19-24, and 125I-labeled 19-24
immunoconjugate was also evaluated over a 24-h period in
tumor and normal tissues of athymic mice bearing a human
fibrosarcoma xenograft. Poor uptake of radiolabeled
Adriamycin by the
tumor tissue was observed. The level of 14C 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 characterized by the high
tumor tissue:blood ratio of 1.62 +/- 0.28 (SD). However, for
monoclonal antibody 19-24
immunoconjugates, this ratio decreased 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
monoclonal antibody P3
immunoconjugates (0.22 +/- 0.03). Thus, it appears that, compared to free
daunomycin,
monoclonal antibody 19-24
immunoconjugates may be more efficient and less cytotoxic to normal tissues.