Immunological responses in cancer patients after vaccination with the therapeutic telomerase-specific vaccine Vx-001.

Vx-001, an HLA-A*0201 restricted telomerase (TERT)-specific anti-tumor vaccine, is composed of the 9-mer cryptic TERT(572) peptide and its optimized variant TERT(572Y). We have previously shown that Vx-001 is non-toxic, highly immunogenic and in vaccinated NSCLC patients early specific immune response is associated with prolonged survival. The aim of the present study was to investigate the specific T-cell immune response against Vx-001. Fifty-five patients with chemo-resistant advanced solid tumors were vaccinated with TERT(572Y) (2 subcutaneous injections) followed by TERT(572) peptide (4 subcutaneous injections) every 3 weeks. Specific immune response was evaluated by IFN-γ and perforin ELISpot and intracellular cytokine staining assays. TERT-reactive T cells were detected in 27 (51%) out of 53 evaluable patients after the 2nd vaccination and in 22 (69%) out of 32 evaluable patients after the completion of 6 vaccinations. Immune responses developed irrespective of the stage of disease and disease status before vaccination. Patients with disease progression at study entry who developed a post-vaccination-induced immunological response had a significant overall survival benefit compared to the post-vaccination non-responders. The Vx-001 vaccine is a promising candidate for cancer immunotherapy since it can induce a TERT-specific T-cell immune response that is associated with prolonged survival.

Sequential administration of the native TERT572 cryptic peptide enhances the immune response initiated by its optimized variant TERT(572Y) in cancer patients.

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 TERT(572Y) to elicit specific T cell immune responses in cancer patients. Forty-eight cancer patients with chemo-resistant tumors received 2 subcutaneous injections of TERT(572Y) at 2 mg followed at random by 4 subcutaneous injections of either TERT572 or TERT(572Y) peptides at 2 mg every 3 weeks. Specific immune response was evaluated by interferon-γ 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 TERT(572Y) vaccinations. These results demonstrate that the best vaccination schedule involves first the administration of the optimized TERT(572Y) followed by the native TERT572 peptides in patients who are candidates for cancer immunotherapy.