Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma

Jonathan Cebon, Elke Jäger, Mark J. Shackleton, Peter Gibbs, Ian D. Davis, Wendie Hopkins, Sharen Gibbs, Qiyuan Chen, Julia Karbach, Heather Jackson, Duncan P. MacGregor, Sue Sturrock, Hilary Vaughan, Eugene Maraskovsky, Antje Neumann, Eric Hoffman, Mathew L. Sherman, Alexander Knuth

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Preclinical studies have shown that low dose IL-12 can potentiate cytotoxic lymphocyte responses. Since previous trials have demonstrated significant toxicity from high dose recombinant human IL-12 (rhIL-12), we sought to determine an optimal biological dose for rhIL-12 at lower doses when combined with peptide antigens. Two studies were undertaken. The rhIL-12 was administered at doses of 0 (placebo), 10, 30 and 100 ng/kg, subcutaneously in one study and intravenously in the other. Apart from IL-12 dosing, the studies were identical. Subjects had evaluable stage III or IV melanoma which expressed Melan-A by RT-PCR or immunohistochemistry. Melan-A26-35 (EAAGIGILTV) and influenza matrix58-66 (GILGFVFTL) peptides were administered intradermally on weeks 1, 2, 3, 4 and 9. Twenty-eight subjects were enrolled, of whom 24 were evaluable for clinical and immunological responses. Therapy was well tolerated, the main adverse event being influenza-like symptoms. Immunological monitoring included the evaluation of cutaneous reactions and assays for antigen-specific T-cells. Clinical responses included a complete response in a subject with small volume subcutaneous disease, a partial response in a subject with hepatic metastases, and mixed responses in pulmonary, pleural and nodal disease. Biopsies of accessible tumors showed infiltration with CD4+ and CD8+ lymphocytes capable of lysing Melan-A peptide-pulsed targets in vitro. No clear dose-dependent effect of rhIL-12 could be determined. The rhIL-12 given either s.c. or i.v. was well tolerated at doses of 10-100 ng/kg. Clinical and immunological activity has been observed in this study where peptides were administered either with or without low dose rhIL-12.

Original languageEnglish
Pages (from-to)1-18
Number of pages18
JournalCancer Immunity
Publication statusPublished - 16 Jul 2003


  • Clinical trial
  • IL-12
  • Immunological monitoring
  • Melan-A peptide
  • Melanoma
  • Vaccination

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