Today, there are more than 40 peptides on the pharmaceutical world market and more than 100 in several clinical phases. Although in the past the pharmaceutical industries had reduced their interest in peptides research, in recent decades, they have rekindled their interest in peptides as a result of contemporary novel technological accomplishments, strategic developments, advances in the areas of formulation and enhanced drug delivery technology of peptides. Thus, eight new peptide drugs that could previously have been characterized as difficult to prepare on the large scale required by industry, have entered the pharmaceutical market at the new millennium. The manufacturing of most of these drugs has benefited from new technological advances. Traditional and most modern techniques have been applied to the manufacture of these new entries. Recent accomplishments, together with the traditional benefits of peptides (high biological activity, high specificity and low toxicity), have led pharmaceutical companies to re-focus their attention on peptide-based agents. Therefore, several serious diseases can be treated using the potential next generation of peptide drugs.

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.

Objective: It was the aim of this study to evaluate the safety of the optimized cryptic peptide TERT572Y in pretreated patients with advanced cancer. Methods: Nineteen patients with progressive and chemotherapy-refractory tumors received escalated doses (2–6 mg) of 2 subcutaneous injections of the optimized TERT572Y peptide followed by 4 subcutaneous injections of the native TERT572 peptide every 3 weeks. Both TERT peptides were coinjected with adjuvant Montanide ISA51. Toxicity was evaluated every 3 weeks and peptide-specific CD8+ cells were detected by flow cytometry using TERT572Y tetramers. Results: Fourteen out of 19 patients completed the vaccination program. No grade III/IV toxicity was observed. Grade I anemia was observed in 4 patients and local skin reaction at the injection site in 11 patients. Other nonhematologic toxicities were mild, and no late toxicity was observed after a median postvaccination follow-up period of 10.7 months. There was no dose-limiting toxicity. Peripheral blood TERT572Y-specific CD8+ lymphocytes were detected in 13 out of 14 evaluable patients after 2 injections with the optimized TERT572Y peptide. There was no complete or partial response, but 4 patients (21%) with persistent TERT572Y-specific CD8+ experienced stable disease for a median of 10.5 months. Conclusion: TERT572Y peptide vaccine is well tolerated and effective in eliciting specific TERT572Y CD8+ lymphocytes in pretreated cancer patients, demonstrating that cryptic peptides could be used in cancer immunotherapy.