Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma

J Clin Oncol. 2001 Sep 15;19(18):3836-47. doi: 10.1200/JCO.2001.19.18.3836.

Abstract

Purpose: Forty-eight patients with high-risk re-sected stage III or IV melanoma were immunized with two tumor antigen epitope peptides derived from gp100(209-217)(210M) (IMDQVPSFV) and tyrosinase(368-376)(370D) (YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients received peptides/IFA with or without interleukin (IL)-12 30 ng/kg to evaluate the toxicities and immune responses in either arm with time to relapse and survival as secondary end points.

Patients and methods: Immunizations were administered every 2 weeks for 8 weeks, then every 4 weeks for 12 weeks, and then once 8 weeks later. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was done before and after vaccination. Skin testing with peptides and recall reagents was performed before and after vaccinations.

Results: Local pain and granuloma formation, fever, and lethargy of grade 1 or 2 were observed. Transient vaccine-related grade 3-but no grade 4-toxicity was observed. Thirty-four of 40 patients developed a positive skin test response to the gp100 peptide but none to tyrosinase. Immune responses were measured by release of gamma-interferon in an enzyme-linked immunosorbent assay (ELISA) by effector cells in the presence of peptide-pulsed antigen-presenting cells or by an antigen-specific tetramer flow cytometry assay. Thirty-three of 38 patients demonstrated an immune response by ELISA after vaccination, as did 37 of 42 patients by tetramer assay. Twenty-four of 48 patients relapsed with a median follow-up of 20 months, and 10 patients in this high-risk group have died.

Conclusion: These data suggest a significant proportion of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine and indicate that IL-12 may increase the immune response and supporting further development of IL-12 as a vaccine adjuvant.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Chemotherapy, Adjuvant
  • Female
  • Freund's Adjuvant
  • Humans
  • Interferon-gamma / analysis
  • Interleukin-12 / therapeutic use*
  • Leukapheresis
  • Lipids*
  • Male
  • Melanoma / blood
  • Melanoma / pathology
  • Melanoma / prevention & control*
  • Melanoma / surgery
  • Middle Aged
  • Monocytes / immunology
  • Neoplasm Staging
  • Skin Neoplasms / blood
  • Skin Neoplasms / pathology
  • Skin Neoplasms / prevention & control*
  • Skin Neoplasms / surgery
  • Skin Tests
  • Survival Analysis
  • Time Factors
  • Vaccination

Substances

  • Cancer Vaccines
  • Lipids
  • incomplete Freund's adjuvant
  • Interleukin-12
  • Interferon-gamma
  • Freund's Adjuvant