Surface antigens of human melanoma cells cultured in serum-free medium: induction of expression of major histocompatibility complex class II antigens.

Previous studies from our laboratory have suggested that melanomas can be grouped in subsets reflecting stages of melanocyte differentiation. Each of these stages has a characteristic cell surface antigenic phenotype. We have examined the effect of culture of melanoma cell lines representing different stages of differentiation in RPMI medium containing insulin, transferrin, and selenium (ITS). Only cell lines with a phenotype corresponding to early or intermediate stages of melanocyte differentiation could be adapted to culture in ITS medium. ITS cultures showed a decreased reactivity with monoclonal antibodies detecting epidermal growth factor receptor and transferrin receptor. Decreased reactivity with anti-epidermal growth factor receptor antibodies was the result of the production of epidermal growth factor receptor-binding molecules by melanoma cells and down-regulation of the receptor, while decreased cell surface expression of transferrin receptors seemed related to redistribution of receptor molecules to an intracellular pool. Culture of Ia-negative melanomas in ITS medium resulted in expression of major histocompatibility complex Class II antigens. Induction of Ia antigen by culture in ITS medium was constitutive and irreversible. No coordinate changes in phenotypic traits suggestive of induction of differentiation were observed. Melanoma cell lines respond differentially to growth factors, and expression of growth factor receptors and other cell surface molecules is regulated by culture conditions.

Mouse monoclonal IgG3 antibody detecting GD3 ganglioside: a phase I trial in patients with malignant melanoma.

R24 is an IgG3 mouse monoclonal antibody that identifies GD3, a prominent ganglioside on the surface of melanoma cells and other cells of neuroectodermal origin. Twelve patients with metastatic melanoma were treated with R24 at three dose levels, 8, 80, or 240 mg/m2, over a period of 2 weeks. Peak antibody levels in the serum were dose related and ranged from less than 0.1 to 62 micrograms/ml. Inflammatory reactions (urticaria, pruritus, erythema, subcutaneous ecchymoses) were observed around tumor sites in patients treated at doses greater than or equal to 80 mg/m2. Tumor biopsies during and after treatment showed lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition. Side effects were mild and were readily controlled by antihistamines. Major tumor regression has been observed in three patients.