title: Alum with interleukin-12 augments immunity to a melanoma peptide vaccine: correlation with time to relapse in patients with resected high-risk disease.
abstract: OBJECTIVE
  We attempted to augment immunity to melanoma antigens using interleukin-12 (IL-12) with aluminum hydroxide (alum) for sustained release or granulocyte macrophage colony-stimulating factor (GM-CSF) added to a multipeptide vaccine.
  
  
  METHODS
  Sixty patients with high-risk resected melanoma were randomized to receive melanoma peptides gp100(209-217) (210M), MART-1(26-35) (27L), and tyrosinase(368-376) (370D) with adjuvant Montanide ISA 51 and either IL-12 at 30 ng/kg with alum (group A), IL-12 at 100 ng/kg with alum (group B), or IL-12 at 30 ng/kg with 250 mug GM-CSF (group C).
  
  
  RESULTS
  Three patients had stage IIC (5%), 50 had stage III (83%), and 7 had stage IV (12%) melanoma. Most toxicities were grade 1/2 and resolved rapidly. Significant toxicity included grade 3 colitis and visual changes and grade 3 headache resolving after stopping IL-12 but continuing peptide vaccine. A higher rate of post-vaccine 6-month immune response to gp100 and MART-1 was observed in group A (15 of 19) or B (19 of 20) that received IL-12 plus alum versus group C with IL-12/GM-CSF (4 of 21; P < 0.001). Post-vaccine enzyme-linked immunospot response rates to peptide analogues in group B were higher than group A (P = 0.031 for gp100 and P = 0.010 for MART-1); both were higher than group C (P < 0.001 for gp100 and P < 0.026 for MART-1). With a median of 24 months of follow-up, 23 patients have relapsed. Post-vaccine immune response to MART-1 was associated with relapse-free survival (P = 0.012).
  
  
  CONCLUSIONS
  IL-12 with alum augmented an immune response to melanoma antigens compared with IL-12 with GM-CSF. Immune response was associated with time to relapse.
authors.affiliation: The Angeles Clinic and Research Institute, Santa Monica, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Jolie C
authors.initials: JC
authors.lastname: Solomon
authors.forename: Ronald
authors.initials: R
authors.lastname: Scotland
authors.forename: Marile
authors.initials: M
authors.lastname: Garcia
authors.forename: Shirley
authors.initials: S
authors.lastname: Sian
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Susan L
authors.initials: SL
authors.lastname: Groshen
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Weber
mesh_terms: D000368:Aged; D000534:Alum Compounds / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D012008:Recurrence; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000494:pharmacology*
chemical_list: D000534:Alum Compounds; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D018664:Interleukin-12; C041524:aluminum sulfate