title: Clinical outcome of patients with various advanced cancer types vaccinated with an optimized cryptic human telomerase reverse transcriptase (TERT) peptide: results of an expanded phase II study.
abstract: BACKGROUND
  TERT (telomerase reverse transcriptase) plays a critical role in tumor cell growth and survival. In an expanded phase II study, we evaluated the immunological and clinical responses to the TERT-targeting Vx-001 vaccine in patients with advanced solid tumors.
  
  
  METHODS
  HLA-A*0201-positive patients received two subcutaneous injections of the optimized TERT(572Y) peptide followed by four injections of the native TERT(572) peptide, every 3 weeks. Peptide-specific immune responses were evaluated by enzyme-linked immunosorbent spot at baseline, and after the second and the sixth vaccinations.
  
  
  RESULTS
  Fifty-five patients were enrolled and 34 (62%) completed the six vaccinations. A TERT-specific T-cell immune response was observed in 55% and 70% of patients after the second and the sixth vaccinations, respectively. The disease control rate (DCR) was 36% [95% confidence interval (CI) 24% to 49%], including one complete and one partial response. Immunologically responding patients had a better clinical outcome than nonresponders [DCR: 44% versus 14% (P = 0.047); progression-free survival (PFS): 5.2 versus 2.2 months (P = 0.0001) and overall survival: 20 versus 10 months (P = 0.041)]. Multivariate analysis revealed that the immunological response was an independent variable associated with increased PFS (hazard ratio = 3.35; 95% CI 1.7-6.7).
  
  
  CONCLUSIONS
  Vx-001 vaccine was well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.
authors.affiliation: Department of Medical Oncology, University Hospital of Heraklion, Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
authors.forename: E-K
authors.initials: EK
authors.lastname: Vetsika
authors.forename: S
authors.initials: S
authors.lastname: Christou
authors.forename: D
authors.initials: D
authors.lastname: Hatzidaki
authors.forename: N
authors.initials: N
authors.lastname: Vardakis
authors.forename: D
authors.initials: D
authors.lastname: Aggouraki
authors.forename: G
authors.initials: G
authors.lastname: Konsolakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Ch
authors.initials: Ch
authors.lastname: Christophyllakis
authors.forename: P
authors.initials: P
authors.lastname: Cordopatis
authors.forename: K
authors.initials: K
authors.lastname: Kosmatopoulos
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019098:Telomerase / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D019098:Telomerase; C521181:telomerase reverse transcriptase p572Y, human