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Vaccination with long NY-ESO-1 79-108 peptide and CpG-B leads to robust activation of CD4 and CD8 T cell responses in stage III/IV melanoma patients, and a new HLA-DR7 epitope
  1. Petra Baumgartner1,
  2. Carla Costa Nunes2,
  3. Amélie Cachot2,
  4. Hélène Maby-El Hajjami3,
  5. Laurène Cagnon4,
  6. Marion Braun5,
  7. Laurent Derré6,
  8. Jean-Paul Rivals7,
  9. Donata Rimoldi2,
  10. Emanuela Romano4,
  11. Olivier Michielin8,
  12. Pedro Romero3,
  13. Camilla Jandus2 and
  14. Daniel E Speiser3
  1. Aff1 grid.8515.90000000104234662Ludwig Center for Cancer Research at the University of Lausanne and Department of OncologyUniversity Hospital of Lausanne Lausanne Switzerland
  2. Aff2 grid.9851.50000000121654204Ludwig Cancer Research CenterUniversity of Lausanne Lausanne Switzerland
  3. Aff3 grid.9851.50000000121654204Department of Oncology, Ludwig Cancer Research CenterUniversity of Lausanne Lausanne Switzerland
  4. Aff4 grid.8515.90000000104234662Department of OncologyUniversity Hospital Center (CHUV) Lausanne Switzerland
  5. Aff5 Miltenyi Biotech GmbH Bergisch Galdbach Germany
  6. Aff6 grid.8515.90000000104234662Urology Research Unit, Urology DepartmentUniversity Hospital Center (CHUV) Lausanne Switzerland
  7. Aff7 grid.8515.90000000104234662Department of Otolaryngology, Head and Neck SurgeryUniversity Hospital Center (CHUV) Lausanne Switzerland
  8. Aff8 grid.8515.90000000104234662Centre Hospitalier Universitaire Vaudois Lausanne Switzerland

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Meeting abstracts

Although promising, the combination of long synthetic peptides and CpG-B oligodeoxynucleotides has not yet been tested as cancer vaccine. 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-ESO79-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced responses of both CD8 and CD4 T cells, starting early after initiation of immunotherapy and lasting for many months. The T cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patient's HLAs. The most immunogenic region of the vaccine peptide was the NY-ESO-183-97 sequence, inducing HLA-DR or -DP restricted CD4 T cell responses in all patients tested. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 5/5 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-179-108 peptide combined with the strong immune adjuvant CpG-B, a TLR-9 agonist, induced integrated, robust and functional CD8 and CD4 T cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.