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

Purpose: Forty-eight patients with high-risk resected stage III or IV melan oma were immunized with two tumor antigen epitope peptides derived from gp1 00(209-217)(210M) (IMDQVPSFV) and tyrosinase (368-376)(370D) (YMDGTMSOV) em ulsified with incomplete Freund's adjuvant (IFA). Patients received peptide s/IFA with or without interleukin (IL)-1230 ng/kg to evaluate the toxicitie s and immune responses in either arm with time to relapse and survival as s econdary end points. Patients and Methods: Immunizations were administered every 2 weeks for 8 w eeks, then every 4 weeks for 12 weeks, and then once 8 weeks later. A leuka pheresis to obtain peripheral-blood mononuclear cells for immune analyses w as 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-toxi city was observed. Thirty-four of 40 patients developed a positive skin tes t response to the gp 100 peptide but none to tyrosinase. immune responses w ere measured by release of gamma-interferon in an enzyme-linked immunosorbe nt assay (ELISA) by effector cells in the presence of peptide-pulsed antige n-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 re sected melanoma mount an antigen-specific immune response against a peptide vaccine and indicate that IL-12 may increase the immune response and suppo rting further development of IL-12 as a vaccine adjuvant. J Clin Oncol 19:3 836-3847. (C) 2001 by American Society of Clinical Oncology.