Melanoma targeting with a cocktail of monoclonal antibodies to distinct determinants of the human HMW-MAA.

The monoclonal antibodies (MoAbs) 149.53, 225.28, and 763.74 which recognize distinct and spatially distant determinants of the human high molecular weight-melanoma associated antigen (HMW-MAA) do not influence the binding of each other to cultured human melanoma cells. In vitro incubation of melanoma cells with a combination of the three 125I-labeled anti-HMW-MAA MoAbs results in a marked additive binding only when the MoAbs are used at saturating concentrations. Injection of the combination of the three 125I-labeled MoAbs (up to 300 micrograms per mouse) into human melanoma-bearing nude mice does not increase the amount of radioactivity specifically localized in melanoma lesions above the level observed upon injection of corresponding doses of individual MoAbs. These results may reflect the low concentration of MoAbs which reaches tumor lesions in vivo. Therefore, administration of combinations of MoAbs to distinct determinants of HMW-MAA may not increase the sensitivity of immunoscintigraphy to visualize lesions in patients with melanoma.