title: 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-179-108peptide 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-189-102for CD8+and NY-ESO-183-99for CD4+T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 7/7 HLA-DR7+patients generated strong CD4+T-cell responses, as detected directlyex vivowith fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179-108peptide 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.
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Baumgaertner
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Costa Nunes
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Cachot
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Maby-El Hajjami
authors.affiliation: Department of Oncology, University Hospital Center (CHUV) , Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Cagnon
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Braun
authors.affiliation: Urology Research Unit, Urology Department, University Hospital Center (CHUV) , Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Derré
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, CHUV, University of Lausanne , Switzerland.
authors.forename: J-P
authors.initials: JP
authors.lastname: Rivals
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Rimoldi
authors.affiliation: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai , New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gnjatic
authors.affiliation: Department of Oncology, University Hospital Center (CHUV) , Lausanne, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Abed Maillard
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Marcos Mondéjar
authors.affiliation: Tumor Immunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Protti
authors.affiliation: Department of Oncology, University Hospital Center (CHUV) , Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Romano
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Michielin
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Romero
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.affiliation: Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Jandus
keywords: CpG-B; HLA-DR7; NY-ESO-1; long synthetic peptide; malignant melanoma