Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8 ⁺ and CD4 ⁺ T-cell responses with multiple specificities including a novel DR7-restricted epitope

ABSTRACT

Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1–12) monthly vaccines s.c. composed of the long synthetic NY-ESO-1 _79–108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8 ⁺ and CD4 ⁺ T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-1 _89–102 for CD8 ⁺ and NY-ESO-1 _83–99 for CD4 ⁺ T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-1 _87–99); 7/7 HLA-DR7 ⁺ patients generated strong CD4 ⁺ T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-1 _79–108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8 ⁺ and CD4 ⁺ T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.