title: Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma.
abstract: BACKGROUND
  Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.
  
  
  METHODS
  This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).
  
  
  RESULTS
  Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.
  
  
  CONCLUSIONS
  Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
authors.affiliation: Department of Dermatology, Medical University Graz, Auenbruggerplatz 8, 8010, Graz, Austria. juergen.becker@medunigraz.at
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Mads H
authors.initials: MH
authors.lastname: Andersen
authors.forename: Valeska
authors.initials: V
authors.lastname: Hofmeister-Müller
authors.forename: Marion
authors.initials: M
authors.lastname: Wobser
authors.forename: Lidia
authors.initials: L
authors.lastname: Frey
authors.forename: Christiane
authors.initials: C
authors.lastname: Sandig
authors.forename: Steffen
authors.initials: S
authors.lastname: Walter
authors.forename: Harpreet
authors.initials: H
authors.lastname: Singh-Jasuja
authors.forename: Eckhart
authors.initials: E
authors.lastname: Kämpgen
authors.forename: Andreas
authors.initials: A
authors.lastname: Opitz
authors.forename: Marc
authors.initials: M
authors.lastname: Zapatka
authors.forename: Eva-B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Per
authors.initials: P
authors.lastname: Thor Straten
authors.forename: David
authors.initials: D
authors.lastname: Schrama
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D015788:HLA-A1 Antigen / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D015797:HLA-B35 Antigen / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000276:immunology; D012737:Sex Factors; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D015797:HLA-B35 Antigen; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D000077022:Survivin; D022223:Vaccines, Subunit