Sequential Administration of the Native TERT572 Cryptic Peptide Enhances the Immune Response Initiated by its Optimized Variant TERT572Y in Cancer Patients

Summary: The aim of this study was to investigate the best administration of telomerase reverse transcriptase (TERT572), an human leukocyte antigen-A*0201-restricted cryptic epitope of telomerase, and its optimized variant TERT572Y to elicit specific T cell immune responses in cancer patients. Forty-eight cancer patients with chemo-resistant tumors received 2 subcutaneous injections of TERT572Y at 2 mg followed at random by 4 subcutaneous injections of either TERT572 or TERT572Y peptides at 2 mg every 3 weeks. Specific immune response was evaluated by interferon-g enzyme-linked immunosorbent spot. T cell responses after the sixth vaccination were detected more frequently (44% vs. 17%), and with higher number of peptide-specific reactive T cells (60 T cells/2� 10 5 peripheral blood mononuclear cell vs. 10 T cells/ 2� 10 5 peripheral blood mononuclear cell, P = 0.04), and higher avidity in the patients who received 4 more vaccinations with the TERT572 peptide compared with patients who received only TERT572Y vaccinations. These results demonstrate that the best vaccination schedule involves first the administration of the optimized TERT572Y followed by the native TERT572 peptides in patients who are candidates for cancer immunotherapy.