title: Vaccination of patients with advanced non-small-cell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide.
abstract: OBJECTIVE
  To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) presented by HLA-A*0201 in patients with advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Twenty-two patients with advanced NSCLC and residual (n = 8) or progressive disease (PD; n = 14) following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide administered every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay and/or TERT572Y pentamer staining.
  
  
  RESULTS
  Twelve (54.5%) of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) of 21 patients after the second vaccination, and 10 (90.9%) of 11 patients after the sixth vaccination. Stable disease (SD) occurred in eight (36.4%) of 22 vaccinated patients, with three (13.6%) having had PD before entering the study. The median duration of SD was 11.2 months. After a median follow-up of 10.0 months, patients with early developed immunological response (n = 16) had a significantly longer time to progression and overall survival (OS) than nonresponders (n = 5; log-rank tests P = .046 and P = .012, respectively). The estimated median OS was 30.0 months (range, 2.8 to 40.0 months) and 4.1 months (range, 2.4 to 10.9 months) for responders and nonresponders, respectively.
  
  
  CONCLUSIONS
  TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. Immunological response is associated with prolonged survival. These results are encouraging and warrant further evaluation in a randomized study.
authors.affiliation: Department of Transfusion Medicine, University General Hospital of Heraklion, Heraklion, Crete, Greece.
authors.forename: Irini
authors.initials: I
authors.lastname: Bolonaki
authors.forename: Athanassios
authors.initials: A
authors.lastname: Kotsakis
authors.forename: Elsa
authors.initials: E
authors.lastname: Papadimitraki
authors.forename: Despoina
authors.initials: D
authors.lastname: Aggouraki
authors.forename: George
authors.initials: G
authors.lastname: Konsolakis
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Vagia
authors.forename: Charalambos
authors.initials: C
authors.lastname: Christophylakis
authors.forename: Irini
authors.initials: I
authors.lastname: Nikoloudi
authors.forename: Elefterios
authors.initials: E
authors.lastname: Magganas
authors.forename: Athanassios
authors.initials: A
authors.lastname: Galanis
authors.forename: Paul
authors.initials: P
authors.lastname: Cordopatis
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000368:Aged; D019496:Cancer Vaccines; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry*; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D019098:Telomerase; C521181:telomerase reverse transcriptase p572Y, human