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

P Baumgaertner; C Costa Nunes; A Cachot; H Maby-El Hajjami; L Cagnon; M Braun; L Derré; J-P Rivals; D Rimoldi; S Gnjatic; S Abed Maillard; P Marcos Mondéjar; M P Protti; E Romano; O Michielin; P Romero; D E Speiser; C Jandus

doi:10.1080/2162402X.2016.1216290

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

Oncoimmunology. 2016 Sep 9;5(10):e1216290. doi: 10.1080/2162402X.2016.1216290. eCollection 2016.

Authors

P Baumgaertner¹, C Costa Nunes¹, A Cachot¹, H Maby-El Hajjami², L Cagnon³, M Braun¹, L Derré⁴, J-P Rivals⁵, D Rimoldi¹, S Gnjatic⁶, S Abed Maillard³, P Marcos Mondéjar², M P Protti⁷, E Romano³, O Michielin², P Romero², D E Speiser², C Jandus¹

Affiliations

¹ Ludwig Cancer Research Center, Department of Oncology, University of Lausanne , Switzerland.
² Ludwig Cancer Research Center, Department of Oncology, University of Lausanne, Switzerland; Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland.
³ Department of Oncology, University Hospital Center (CHUV) , Lausanne, Switzerland.
⁴ Urology Research Unit, Urology Department, University Hospital Center (CHUV) , Lausanne, Switzerland.
⁵ Department of Otorhinolaryngology - Head and Neck Surgery, CHUV, University of Lausanne , Switzerland.
⁶ Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai , New York, USA.
⁷ Tumor Immunology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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.

Keywords: CpG-B; HLA-DR7; NY-ESO-1; long synthetic peptide; malignant melanoma.

Publication types

Research Support, Non-U.S. Gov't