Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients
| Autor: | M R, Albertini, J A, Hank, J H, Schiller, M, Khorsand, A A, Borchert, J, Gan, R, Bechhofer, B, Storer, R A, Reisfeld, P M, Sondel |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Male Dose-Response Relationship Drug Recombinant Fusion Proteins Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Middle Aged Recombinant Proteins Antibodies Anti-Idiotypic Immunophenotyping Tumor Cells Cultured Humans Interleukin-2 Female Immunotherapy Lymphocyte Count Lymphocytes Neoplasm Metastasis Killer Cells Lymphokine-Activated Melanoma |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 3(8) |
| ISSN: | 1078-0432 |
| Popis: | We conducted a Phase IB trial of antidisialoganglioside chimeric 14. 18 (ch14.18) antibody and interleukin 2 (IL-2) to determine the maximal tolerated dose (MTD), immunological effects, antitumor effects, and toxicity of this treatment combination. Twenty-four melanoma patients received immunotherapy with ch14.18 antibody and a continuous infusion of Roche IL-2 (1.5 x 10(6) units/m2/day) given 4 days/week for 3 weeks. The ch14.18 antibody (dose level, 2-10 mg/m2/day) was scheduled to be given for 5 days, before, during, or following initial systemic IL-2 treatment. The ch14.18 MTD was 7.5 mg/m2/day, and 15 patients were treated with the ch14.18 MTD. Immunological effects included the induction of lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity by peripheral blood mononuclear cells. In addition, serum samples obtained following ch14.18 infusions were able to facilitate in vitro antibody-dependent cellular cytotoxicity. Antitumor activity included one complete response, one partial response, eight patients with stable disease, and one patient with50% decrease of hepatic metastases in the face of recurrence of a s.c. lesion. Dose-limiting toxicities were a severe allergic reaction and weakness, pericardial effusion, and decreased performance status. Most patients treated at the MTD had abdominal, chest, or extremity pain requiring i.v. morphine. One patient had an objective peripheral neuropathy. This IL-2 and ch14.18 treatment combination induces immune activation in all patients and antitumor activity in some melanoma patients. We are attempting to enhance this treatment approach by addition of the anti-GD3 R24 antibody to this IL-2 and ch14.18 regimen. |
| Databáze: | OpenAIRE |
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