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Augmented Binding of Radiolabeled Monoclonal Antibodies to Melanoma Cells Using Specific Antibody Combinations¹

Department of Clinical Immunology and Biological Therapy, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Antigenic heterogeneity may limit effective cancer therapy using monoclonal antibodies (Mabs). To address this problem, combinations of two, three, or four ¹²⁵I-labeled antimelanoma Mabs (NRML-05, P94, 96.5, and CL207) were incubated in vitro with three different melanoma cell lines (HS294t, A375SM, and DX3). Binding of the various Mab combinations was expressed as total cpm/10⁵ cells and was compared to binding of each Mab alone. Saturating amounts (10 µg/ml) of two, three, or four Mabs bound to a significantly greater extent (P < 0.05) than each individual Mab except for NRML-05. Combinations of three Mabs at a nonsaturating concentration (1.5 µg/ml) bound to a greater extent than single Mabs (P < 0.05), depending on the cell line examined and the amount of antigen sites present for each Mab. Saturating or nonsaturating concentrations of unlabeled Mab 96.5 combined with ¹²⁵I-labeled NRML-05 enhanced binding of the latter to HS294t by significantly modifying its affinity and by increasing the number of binding sites 3-fold. Modulation occurred only at 37°C and was dependent upon protein synthesis. These data demonstrate that the effectiveness of various Mab combinations over single Mabs varies, depending on Mab concentration and the cell lines used. In addition, one Mab may significantly (P < 0.05) enhance binding of another Mab to its antigen.

¹ Supported by USPHS Grant CA43544 from the National Cancer Institute. Research was conducted, in part, by the Clayton Foundation for Research. Presented in abstract form at the Fifth International Conference on Monoclonal Antibody Immunoconjugates for Cancer, March 15–17, 1990, San Diego, CA.

² To whom requests for reprints should be addressed, at University of Texas M. D. Anderson Cancer Center, 1515 Holcombe (Box 041), Houston, TX 77030.

Received 8/23/90. Accepted 3/15/91.