title: Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines for the treatment of patients with metastatic melanoma.
abstract: OBJECTIVE
  Two clinical trials were conducted to evaluate the clinical efficacy and immunologic impact of vaccination against the tyrosinase protein plus systemic interleukin 2 (IL-2) administration in patients with advanced metastatic melanoma.
  
  
  METHODS
  Full-length tyrosinase was employed as an immunogen to induce diverse immunologic responses against a commonly expressed melanoma antigen. Heterologous prime/boost vaccination with recombinant vaccinia and fowlpox vectors encoding tyrosinase was first explored in a randomized three-arm phase II trial, in which vaccines were administered alone or concurrently with low-dose or high-dose IL-2. In a subsequent single cohort phase II trial, all patients received the same vaccines and high-dose IL-2 sequentially rather than concurrently.
  
  
  RESULTS
  Among a total of 64 patients treated on these trials, 8 objective partial responses (12.5%) were observed, all in patients receiving high-dose IL-2. Additional patients showed evidence of lesional regression (mixed tumor response) or overall regression that did not achieve partial response status (minor response). In vitro evidence of enhanced immunity against tyrosinase following protocol treatments was documented in 3 of 49 (6%) patients tested serologically, 3 of 23 (13%) patients tested for T-cell recognition of individual tyrosinase peptides, and 4 of 16 (25%) patients tested for T-cell recognition of full-length tyrosinase protein with real-time reverse transcription-PCR techniques.
  
  
  CONCLUSIONS
  Whereas prime/boost immunization with recombinant vaccinia and fowlpox viruses enhanced antityrosinase immunity in some patients with metastatic melanoma, it was ineffective alone in mediating clinical benefit, and in combination with IL-2 did not mediate clinical benefit significantly different from that expected from treatment with IL-2 alone.
authors.affiliation: Surgery Branch, National Cancer Institute, Center for Cancer Research, NIH, Bethesda, Maryland, USA.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Lindsey
authors.forename: Linda
authors.initials: L
authors.lastname: Gritz
authors.forename: Richard
authors.initials: R
authors.lastname: Sherry
authors.forename: Andrea
authors.initials: A
authors.lastname: Abati
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Fetsch
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Goldfeder
authors.forename: Monica I
authors.initials: MI
authors.lastname: Gonzales
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Zinnack
authors.forename: Linda
authors.initials: L
authors.lastname: Rogers-Freezer
authors.forename: Leah
authors.initials: L
authors.lastname: Haworth
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Mavroukakis
authors.forename: Donald E
authors.initials: DE
authors.lastname: White
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Panicali
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D003131:Combined Modality Therapy; D004274:DNA, Recombinant / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009362:Neoplasm Metastasis; D011212:Poxviridae / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*
chemical_list: D019496:Cancer Vaccines; D004274:DNA, Recombinant; D007074:Immunoglobulin G; D007376:Interleukin-2; D012333:RNA, Messenger; D007371:Interferon-gamma; D014442:Monophenol Monooxygenase