Melanoma antibodies: specificity and interaction with melanoma and cytotoxic T-cells

Six antigenic systems on melanoma cell surfaces have been defined by monoclonal antibodies. The disialoganglioside GD3, detected by mAb R-24, was found to be strongly expressed on most melanoma cell surfaces, but weakly on normal melanocytes and some astrocytomas as determined by serological methods. Epithelial cell types, fibroblasts and cells of hematopoietic origin did not react. Frozen sections of primary and metastatic malignant melanoma stained positive in 60/62 cases by immunofluorescence and immunoperoxidase. In vitro studies with seven antibodies to seven melanoma cell surface antigens revealed blocking of melanoma cell growth by monoclonal anti-GD3-antibody R-24 only. GD3-expression varies greatly in human malignant melanoma cells. Six melanoma cell lines, expressing high levels of GD3 on the cell surface, as determined by quantitative absorption studies, showed growth inhibition in the presence of R-24 antibody. Four melanoma cell lines, however, with low GD3-expression and seven GD3-negative non-melanoma cells types remained unaffected by mAbR-24. In addition, this monoclonal anti-GD3-antibody efficiently blocked T-cell cytotoxicity for autologous malignant melanoma cells in culture. Cytotoxicity of autologous cloned T-lymphocytes, cytotoxic for the autologous melanoma cell line and crossreactive with a hypernephroma line was specifically blocked by mAbR-24 on the level of the GD3-expressing target. In an ongoing phase I clinical study, the toxicity of mAbR-24 was evaluated. So far two patients tolerated antibody infusions without adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS)