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/m2 versus 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.
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.