Clinical StudiesSequential Administration of the Native TERT572 Cryptic Peptide Enhances the Immune Response Initiated by its Optimized Variant TERT572Y in Cancer PatientsVetsika, Eleni-Kyriaki*; Papadimitraki, Elisavet*; Aggouraki, Despoina*; Konsolakis, Georgios*; Mela, Marina-Eleni*; Kotsakis, Athanasios†; Christou, Soultana†; Patramani, Stefania†; Alefantinou, Marina†; Kaskara, Ageliki‡; Christophyllakis, Charalampos‡; Kosmatopoulos, Kostas§; Georgoulias, Vassilis*,†,‡; Mavroudis, Dimitris*,†Author Information *Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion †Department of Medical Oncology, University General Hospital of Heraklion, Crete ‡First Department of Medical Oncology, “IASO” General Hospital of Athens, Athens, Greece §INSERM, Paris, France E.-K. V. and E. P. contributed equally to this work. This research was supported by grants in part by the Cretan Association for Biomedical Research (CABR) and in part by the Research Committee in Greece. Reprints: Eleni-Kyriaki Vetsika, Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Voutes, Heraklion, 71110 Crete, Greece (e-mail: email@example.com). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site, www.immunotherapy-journal.com. Received February 1, 2011 Accepted July 31, 2011 Journal of Immunotherapy: November-December 2011 - Volume 34 - Issue 9 - p 641–650 doi: 10.1097/CJI.0b013e31823284a6 Buy SDC Metrics AbstractIn Brief The aim of this study was to investigate the best administration of telomerase reverse transcriptase (TERT572), an human leukocyte antigen-A*0201-restricted cryptic epitope of telomerase, and its optimized variant TERT572Y to elicit specific T cell immune responses in cancer patients. Forty-eight cancer patients with chemo-resistant tumors received 2 subcutaneous injections of TERT572Y at 2 mg followed at random by 4 subcutaneous injections of either TERT572 or TERT572Y peptides at 2 mg every 3 weeks. Specific immune response was evaluated by interferon-γ enzyme-linked immunosorbent spot. T cell responses after the sixth vaccination were detected more frequently (44% vs. 17%), and with higher number of peptide-specific reactive T cells (60 T cells/2×105 peripheral blood mononuclear cell vs. 10 T cells/2×105 peripheral blood mononuclear cell, P=0.04), and higher avidity in the patients who received 4 more vaccinations with the TERT572 peptide compared with patients who received only TERT572Y vaccinations. These results demonstrate that the best vaccination schedule involves first the administration of the optimized TERT572Y followed by the native TERT572 peptides in patients who are candidates for cancer immunotherapy. Supplemental Digital Content is available in the text. © 2011 Lippincott Williams & Wilkins, Inc.