Antitumor effects of antibodies against ganglioside antigens of melanoma have been reported, but neither optimal doses nor mechanisms have been established.

This Phase IB trial of the murine immunoglobulin IgG₃ monoclonal antibody R₂₄ against disialoganglioside GD3 was conducted with 37 patients to define better the dose‐response relation and mechanism of action of R₂₄ in patients with metastatic melanoma.

Dose‐limiting toxicity consisted of a pulmonary capillary leak syndrome in 3 of 5 patients in the 80 mg/M²/day dosage tier. Serial blood and tumor biopsy samples were obtained prior to therapy and on Days 5, 9, and 22 following R₂₄ infusion. Tumor biopsy‐infiltrating lymphocytes were enumerated in peritumoral, endotumoral, and perivascular compartments: endotumoral CD4⁺ and CD8⁺ T cells and HLA‐DR⁺ T cells increased over time on R₂₄ antibody. Endotumoral CD4 lymphoid infiltrate activation (DR expression) and antibody‐dependent cytotoxicity were the greatest in the one patient who achieved a complete response.

Clinical response was associated with depression in natural killer (CD56⁺ and CD56⁺DR⁺) blood cells (P = 0.03) and was associated with R₂₄ dosage (P = 0.01). A complete response that lasted 2 years and a partial response that lasted 2 months occurred at a dose of 1 mg/M²/day. The limited number of clinical responses observed in this trial hampered the correlation of antitumor and immune parameters but provided a rational foundation for the future evaluation of antiganglioside antibodies. Cancer 2000;88:2693–702. © 2000 American Cancer Society.