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Vaccination of Patients With Advanced Non–Small-Cell Lung Cancer With an Optimized Cryptic Human Telomerase Reverse Transcriptase Peptide

Irini Bolonaki, Athanassios Kotsakis, Elsa Papadimitraki, Despoina Aggouraki, George Konsolakis, Aphrodite Vagia, Charalambos Christophylakis, Irini Nikoloudi, Elefterios Magganas, Athanassios Galanis, Paul Cordopatis, Kostas Kosmatopoulos, Vassilis Georgoulias, Dimitris Mavroudis

From the Departments of Transfusion Medicine, Medical Oncology, and Radiology, University General Hospital of Heraklion; Laboratory of Tumor Biology, School of Medicine, University of Crete, Heraklion, Crete; "Iaso" General Hospital, Athens, Greece; and the Department of Pharmacy, University of Patras, Patras; Vaxon Biotech, Genopole, Evry, France

Address reprint requests to Dimitris Mavroudis, MD, PhD, Department of Medical Oncology, University Hospital of Heraklion, Voutes, 71110, Crete, Greece; e-mail: mavrudis{at}med.uoc.gr

Purpose To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT_572Y) presented by HLA-A*0201 in patients with advanced non–small-cell lung cancer (NSCLC).

Patients and 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 TERT_572Y 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 TERT_572Y 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.

Conclusion TERT_572Y 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.

Supported in part by grants from the Cretan Association for Biomedical Research.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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