The in vitro sensitivity of human
melanoma cell lines to conjugates of whole
abrin or
ricin linked through
disulfide bonds to the monoclonal antimelanoma antibody 9.2.27 was studied. After passage of the conjugates through a
Sepharose 4B column to remove molecular species with exposed binding sites on their B-chains, toxicity of the conjugates to different
melanoma cell lines and nonmelanoma
tumor lines was assessed by measuring their ability to inhibit cellular
protein synthesis. The
abrin conjugate was far more toxic to the target cells than the corresponding
ricin conjugate. The 8
melanoma cell lines studied differed widely in their sensitivities to the
abrin conjugate. The differences were associated with concomitant large differences in the sensitivities of the cells to the native toxins, and the significance of the level of the
antigen expression became apparent only when the sensitivities of the different cell lines were normalized with respect to their sensitivity to native
abrin. The observed relationship could not be accounted for by unspecific binding via the B-chain binding site of the
immunotoxin. The differential sensitivity of the
melanoma cell lines to the
immunotoxin seems to be related to inherent differences between the cells in their ability to internalize and to process
immunotoxins and toxins. The findings may have considerable practical implications.