A Phase I Study of the Optimized Cryptic Peptide TERT<sub>572Y</sub> in Patients with Advanced Malignancies

<i>Objective:</i> It was the aim of this study to evaluate the safety of the optimized cryptic peptide TERT_572Y in pretreated patients with advanced cancer. <i>Methods:</i> Nineteen patients with progressive and chemotherapy-refractory tumors received escalated doses (2–6 mg) of 2 subcutaneous injections of the optimized TERT_572Y 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 TERT_572Y tetramers. <i>Results:</i> 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 TERT_572Y-specific CD8+ lymphocytes were detected in 13 out of 14 evaluable patients after 2 injections with the optimized TERT_572Y peptide. There was no complete or partial response, but 4 patients (21%) with persistent TERT_572Y-specific CD8+ experienced stable disease for a median of 10.5 months. <i>Conclusion:</i> TERT_572Y peptide vaccine is well tolerated and effective in eliciting specific TERT_572Y CD8+ lymphocytes in pretreated cancer patients, demonstrating that cryptic peptides could be used in cancer immunotherapy.