| Abstract: |
A combination of recombinant human interleukin 2 (rhIL2) and mouse monoclonal antibody R24 (recognizing the ganglioside Gdj) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10 units/m 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/m 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/m versus 2239 � 672/ml at doses of 1 and 3 mg/m. This evidence and other data suggested that R24 enhanced lL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for Goj-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 rhlL-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. © 1990, American Association for Cancer Research. All rights reserved. |
| Keywords: |
adult; clinical article; controlled study; aged; middle aged; clinical trial; cell division; interleukin 2; melanoma; metastasis; controlled clinical trial; antineoplastic combined chemotherapy protocols; dose-response relationship, drug; monoclonal antibody; antibodies, monoclonal; leukocytes, mononuclear; recombinant proteins; killer cells, natural; phase 1 clinical trial; lymphocytes; intravenous drug administration; interleukin-2; humans; human; male; female; priority journal; article; killer cells, lymphokine-activated
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