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

Cancer Immun. 2003 Jul 16;3:7.


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-A (26-35) (EAAGIGILTV) and influenza matrix (58-66) (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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm / adverse effects
  • Antigens, Neoplasm / therapeutic use
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use
  • Drug Administration Schedule
  • Drug Hypersensitivity
  • Drug Therapy, Combination
  • Female
  • Humans
  • Influenza A virus / chemistry
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / adverse effects
  • Interleukin-12 / therapeutic use*
  • MART-1 Antigen
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Middle Aged
  • Neoplasm Proteins / adverse effects
  • Neoplasm Proteins / therapeutic use*
  • Peptide Fragments / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use*
  • Viral Matrix Proteins / therapeutic use*


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptide Fragments
  • Recombinant Proteins
  • Viral Matrix Proteins
  • influenza virus membrane protein (58-66)
  • Interleukin-12