A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 × 106 units/m2 i.v. over 6 h on days 1–5 and 8–12. R24 was given on days 8–12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 ± 554/ml in patients treated at R24 doses of 8 and 12 mg/m2versus 2239 ± 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro.

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Supported in part by National Cancer Institute Contract NO1 CM47665, the Alcoa Foundation, and the Louis and Anne Abrons Foundation. D. F. B. is a recipient of an American Cancer Society Clinical Oncology Career Development Award, P. B. C. an American Society of Clinical Oncology Young Investigator Award, and A. N. H. a Cancer Research Institute/Benjamin Jacobson Family Award.

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