title: A phase II trial evaluating the clinical and immunologic response of HLA-A2(+) non-small cell lung cancer patients vaccinated with an hTERT cryptic peptide.
abstract: OBJECTIVE
  The immunological and clinical responses of patients with NSCLC treated, in the context of an expanded action program, with the cryptic hTERT-targeting Vx-001 vaccine are presented.
  
  
  METHODS
  Forty-six HLA-A*0201-positive patients with advanced NSCLC and residual (n=27) or progressive (n=19) disease following front-line treatment received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide, every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay at baseline, and after the 2nd and the 6th vaccinations. Thirty-eight HLA-A*0201-positive matched patients were used as historical controls.
  
  
  RESULTS
  Twenty-three patients (50%) completed the vaccination protocol and 87% received at least two administrations. Twelve patients (26%) without disease progression after the 6th vaccination received boost vaccinations. Three (7%) patients achieved a partial response and 13 (28%) disease stabilization. The disease control rate was significantly higher in patients with non-squamous histology compared to those with squamous-cell histology [n=14 (45%) versus n=2 (13%); p=0.03]. The median progression-free survival (PFS) and overall survival (OS) was 3.8 (range, 0.7-99.4) and 19.8 months (range, 0.7-99.4), respectively. Patients who developed immune response had a numerically higher PFS compared to those who failed to mount any (6.7 versus 2.7 months; p=0.090). However, the median OS for the immune-responders was significantly prolonged compared to non-responders (40.0 versus 9.2 months, respectively; p=0.02). Toxicity was <grade 2.
  
  
  CONCLUSIONS
  Vx-001 vaccine is well tolerated and induced a TERT-specific immunological response, which was significantly correlated with improved clinical outcome.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece. Electronic address: thankotsakis@hotmail.com.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Elisavet
authors.initials: E
authors.lastname: Papadimitraki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Eleni Kyriaki
authors.initials: EK
authors.lastname: Vetsika
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Aggouraki
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece.
authors.forename: Eleftheria Kleio
authors.initials: EK
authors.lastname: Dermitzaki
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece.
authors.forename: Dora
authors.initials: D
authors.lastname: Hatzidaki
authors.affiliation: Department of Medical Oncology, 251 Air Force General Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kentepozidis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Greece; Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D018714:Radiotherapy, Adjuvant; D019098:Telomerase / Q000737:chemistry / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; C509186:TERT protein, human; D019098:Telomerase
keywords: Clinical efficacy; HLA-A2+; Immunologic response; NSCLC; Phase II; h-TERT