title: Active specific immunotherapy of metastatic melanoma with an antiidiotype vaccine: a phase I/II trial of I-Mel-2 plus SAF-m.
abstract: OBJECTIVE
  To determine the toxicity and immunologic activity of an antiidiotype melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-2, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m.
  
  
  METHODS
  Twenty-six patients with metastatic melanoma, 17 of whom had previously received chemotherapy, were given 2 mg of I-Mel-2 and either 100 micrograms (n = 6) or 250 micrograms (n = 20) of SAF-m. Antiidiotype vaccine was given intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 against the melanoma epitope mimicked by the vaccine were titrated before treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging (MRI) of the brain were obtained before and bimonthly during treatment to evaluate responses.
  
  
  RESULTS
  Elevated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical antitumor effect (P = .02 and P = .05, respectively). Ab3 was absent in most patients, but was found in the best clinical responder. Fever, myalgias/arthralgias, fatigue, nausea, and headaches were the most common toxicities. Grade III myalgias/arthralgias and headaches required dose reduction of SAF-m in eight patients at the 250-microgram dose. No treatment-related death occurred. Six patients had an antitumor effect: one complete response in liver and lung, two minor responses, and three stable disease. The patient with a complete response has survived nearly 5 years.
  
  
  CONCLUSIONS
  I-Mel-2 antiidiotype vaccine was safe, tolerated best at the 100-microgram dose of SAF-m, and had immunologic and clinical activity.
authors.affiliation: Center for Biological Therapy and Melanoma Research, University of California, San Diego, La Jolla 92093-0061, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Quan
authors.forename: G E
authors.initials: GE
authors.lastname: Dean
authors.forename: L
authors.initials: L
authors.lastname: Spears
authors.forename: C P
authors.initials: CP
authors.lastname: Spears
authors.forename: S
authors.initials: S
authors.lastname: Groshen
authors.forename: J A
authors.initials: JA
authors.lastname: Merritt
authors.forename: M S
authors.initials: MS
authors.lastname: Mitchell
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C054064:N-acetylmuramyl-threonyl-isoglutamine