A phase I study of the optimized cryptic peptide TERT572Y in patients with advanced malignancies

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 II 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+ lympho- cytes 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. Copyright (c) 2006 S. Karger AG, Basel.