title: Immunological responses in cancer patients after vaccination with the therapeutic telomerase-specific vaccine Vx-001.
abstract: Vx-001, an HLA-A*0201 restricted telomerase (TERT)-specific anti-tumor vaccine, is composed of the 9-mer cryptic TERT(572) peptide and its optimized variant TERT(572Y). We have previously shown that Vx-001 is non-toxic, highly immunogenic and in vaccinated NSCLC patients early specific immune response is associated with prolonged survival. The aim of the present study was to investigate the specific T-cell immune response against Vx-001. Fifty-five patients with chemo-resistant advanced solid tumors were vaccinated with TERT(572Y) (2 subcutaneous injections) followed by TERT(572) peptide (4 subcutaneous injections) every 3 weeks. Specific immune response was evaluated by IFN-γ and perforin ELISpot and intracellular cytokine staining assays. TERT-reactive T cells were detected in 27 (51%) out of 53 evaluable patients after the 2nd vaccination and in 22 (69%) out of 32 evaluable patients after the completion of 6 vaccinations. Immune responses developed irrespective of the stage of disease and disease status before vaccination. Patients with disease progression at study entry who developed a post-vaccination-induced immunological response had a significant overall survival benefit compared to the post-vaccination non-responders. The Vx-001 vaccine is a promising candidate for cancer immunotherapy since it can induce a TERT-specific T-cell immune response that is associated with prolonged survival.
authors.affiliation: Laboratory of Tumor Biology, Medical School, University of Crete, Voutes, 71110, Heraklion, Crete, Greece. vetsika@edu.med.uoc.gr.
authors.forename: Eleni-Kyriaki
authors.initials: EK
authors.lastname: Vetsika
authors.affiliation: Laboratory of Tumor Biology, Medical School, University of Crete, Voutes, 71110, Heraklion, Crete, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Konsolakis
authors.affiliation: Laboratory of Tumor Biology, Medical School, University of Crete, Voutes, 71110, Heraklion, Crete, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Aggouraki
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Elisavet
authors.initials: E
authors.lastname: Papadimitraki
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Soultana
authors.initials: S
authors.lastname: Christou
authors.affiliation: Vaxon Biotech, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Menez-Jamet
authors.affiliation: Vaxon Biotech, Paris, France.
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
authors.affiliation: Laboratory of Tumor Biology, Medical School, University of Crete, Voutes, 71110, Heraklion, Crete, Greece.|Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.|Department of Medical Oncology, "IASO" General Hospital of Athens, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Laboratory of Tumor Biology, Medical School, University of Crete, Voutes, 71110, Heraklion, Crete, Greece.|Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D019098:Telomerase; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D019098:Telomerase; C521181:telomerase reverse transcriptase p572Y, human