Safety and immunogenicity of the optimized cryptic peptide TERT572Y in patients with advanced malignancies: A Phase I clinical study

Abstract

2579 Background: TERT572Y, an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). A phase I trial evaluating the safety and immunogenicity of the cryptic TERT572Y peptide was conducted in HLA-A*0201 cancer patients. Methods: Nineteen patients with chemotherapy refractory and progressing malignant tumors were enrolled in the study. The vaccination protocol consisted of two injections of optimized TERT572Y peptide followed by four injections of native TERT572 peptide. Peptides were injected emulsified in Montanide ISA51. Patients were vaccinated with escalated doses of peptide ranging from 2 to 6 mg. Toxicity and peptide-specific immune responses were evaluated. Results: Fourteen patients completed the entire vaccination program. Only grade I toxicity was observed, affecting 13 of the 19 patients. TERT572Y-specific cytotoxic T cells were detected in the peripheral blood of 13 out of 14 evaluate patients, as early as 3 weeks after the 2nd vaccine injection. CTLs were fully functional and killed TERT-overexpressing tumor cells. Four (29%) of 14 evaluable patients experienced stable disease for a median of 10 months. Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. This is the first clinical trial demonstrating that cryptic peptides are promising candidates for cancer immunotherapy. No significant financial relationships to disclose.